{"id":51436,"date":"2023-09-30T11:04:12","date_gmt":"2023-09-30T11:04:12","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=51436"},"modified":"2023-10-07T09:22:14","modified_gmt":"2023-10-07T09:22:14","slug":"analysis-of-the-development-of-b-cell-precursors-in-day-three-incubated-chicken-embryos","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol16no3\/analysis-of-the-development-of-b-cell-precursors-in-day-three-incubated-chicken-embryos\/","title":{"rendered":"Analysis of the Development of B-Cell Precursors in Day Three Incubated Chicken Embryos"},"content":{"rendered":"\n<p class=\"wp-block-paragraph\"><strong>Introduction<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In\nmammals<sup>1<\/sup> birds <sup>2,3<\/sup> and avian embryos, lymphoid cells of the B lineage,\nwhich are known for their capacity to synthesize immunoglobulin, first emerge.\nFor research on the development of the B-cell repertoire and the establishment\nof self-tolerance, these early B-cell precursors are crucially important<sup>4\u20137<\/sup>. However, little is known about the genetic and\/or\nmicroenvironmental factors that control the onset of immunoglobulin synthesis\nin embryonic haemopoietic cells. Additionally, it appears that B-cell\ndifferentiation begins in such structurally and functionally unrelated organs\nas mammalian fetal liver<sup>4,5<\/sup>. There is disagreement over the exact role the avian\nbursa plays in B-cell differentiation. The development of the humoral immune\nsystem undoubtedly involves the embryonic bursa, as demonstrated by bursectomy\nstudies<sup>2<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The\nearliest immunoglobulin-positive cells that can be found in the chicken embryo\nare also said to be present there. As a result, IgM-containing cells were first\ndiscovered in the follicles of the 14-day embryonic bursa<sup>8<\/sup>. A long-lasting and significant reduction of cellular\nand circulating IgM, IgA, and IgG was also produced by the in vivo injection of\nanti-p antibodies at day 13 in combination with surgical bursectomy at hatching<sup>9<\/sup>. These details were used to show that, in the chicken\nembryo, IgM biosynthesis begins exclusively in the bursal microenvironment, and\nthat B-cell precursors eventually &#8220;switch&#8221; from IgM to IgG to IgA\nsynthesis<sup>9<\/sup> though a &#8220;switch&#8221; from IgM to either IgG or\nIgA cannot be completely ruled out<sup>10<\/sup>. Researchers who discovered residual B-cell\nactivities in bursaless birds have refuted this widely held belief<sup>11<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Therefore,\nthey suggested that B-cell differentiation could take place outside of the\nFabricius bursa, at least in part. Given this debate and our prior findings of\nCLG cells in 12 day bursal mesenchyme<sup>12<\/sup>. In the 11th and 12th day&#8217;s blood as well as the 11,\n12, and 13th day&#8217;s bursal mesenchyme, lymphoid cells were discovered that\ncontained trace amounts of cytoplasmic immunoglobulin. In bursal follicles that\nwere 14 days old, clg large basophilic cells first emerged.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Prebursal stem cells that express the sialyl Lewis X (sLex) carbohydrate epitope and surface IgM reach the bursal anlage epithelium and multiply between embryonic days (ED) 8 and 14, resulting in the formation of nascent lymphoid follicles. The process of immunoglobulin (Ig) heavy- and light-chain diversification by Ig-gene conversion is started by a differentiation event by ED15-17. A change in the growing B-cell surface expression of sLex to a structurally related carbohydrate known as Lewis X (Lex) has been demonstrated to coincide with the commencement of Ig-gene conversion. At ED15\/16 or ED17\/18, respectively, developing B-cells expressing sLex or Lex were isolated from the bursa for functional investigations. Next, PCR amplification of the rearranged Ig light-chain gene was performed in both groups. Ig-gene conversion was started in 76% of the Lex population, but in just 29% of the sLex cells throughout the course of 4 independent trials, according to the DNA sequence of the PCR-amplified Ig light chain. As a result, both phenotypic and functional studies revealed that the embryonic bursa played a significant role in the beginning of repertoire formation through a significant B-cell differentiation event that occurred on or around ED17\/18.<sup>20-22<\/sup> The purpose of these research was The ontogeny of B-cell precursors in chicken embryos from day three of incubation was examined in this work.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Method<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Using\nthe search terms &#8220;ontogeny, B-cell, precursors, chicken embryos,\nincubation,&#8221; a thorough literature search was carried out in the PubMed,\nNCBI, and Google Scholar databases. The publications that were discovered using\nthese keywords were first selected using a variety of inclusion criteria,\nincluding journals that do not accept payments for their articles and research\nfindings that focus on &#8220;ontogeny, B-cell, precursors, chicken embryos,\nincubation.&#8221; Articles that do not meet the inclusion requirements are\nignored, and those that do will be subjected to data analysis.<\/p>\n\n\n<table style=\"width: 70%;\" border=\"1\" cellpadding=\"5\">\n<tbody>\n<tr>\n<td><img decoding=\"async\" class=\"alignnone size-thumbnail wp-image-51444\" src=\"https:\/\/biomedpharmajournal.org\/wp-content\/uploads\/2023\/09\/Vol16No3_Ana_Mas_Fig1-150x150.jpg\" alt=\"\" width=\"150\" height=\"150\" srcset=\"https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2023\/09\/Vol16No3_Ana_Mas_Fig1-150x150.jpg 150w, https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2023\/09\/Vol16No3_Ana_Mas_Fig1-256x256.jpg 256w, https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2023\/09\/Vol16No3_Ana_Mas_Fig1.jpg 801w\" sizes=\"(max-width: 150px) 100vw, 150px\" \/><\/td>\n<td>\n<p><strong>Figure 1: <\/strong><strong>Flow diagram of the search strategy.<\/strong><\/p>\n<p><\/p>\n<p><a href=\"https:\/\/biomedpharmajournal.org\/wp-content\/uploads\/2023\/09\/Vol16No3_Ana_Mas_Fig1.jpg\" target=\"_blank\" rel=\"noopener noreferrer\">Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n<p class=\"wp-block-paragraph\"><strong>Result<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Ontogeny,\nB-cell precursors, chicken embryos, and incubation were the search terms used\nto find 15350 articles in the databases of PubMed, NCBI, and Google Scholar.\nAfter a second round of selection based on the inclusion and exclusion\ncriteria, 38 articles that met the inclusion criteria were retrieved.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Blood from 11 and 12 day embryos had\na small number of lymphoid cells that stained for both cytoplasmic and\nmembrane-bound light chains (figure 2). At different phases of development,\nblood was not examined.<strong><\/strong><\/p>\n\n\n<table style=\"width: 70%;\" border=\"1\" cellpadding=\"5\">\n<tbody>\n<tr>\n<td><img decoding=\"async\" class=\"alignnone size-thumbnail wp-image-51456\" src=\"https:\/\/biomedpharmajournal.org\/wp-content\/uploads\/2023\/09\/Vol16No3_Ana_Mas_Fig2-150x150.jpg\" alt=\"\" width=\"150\" height=\"150\" srcset=\"https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2023\/09\/Vol16No3_Ana_Mas_Fig2-150x150.jpg 150w, https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2023\/09\/Vol16No3_Ana_Mas_Fig2-256x256.jpg 256w, https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2023\/09\/Vol16No3_Ana_Mas_Fig2.jpg 610w\" sizes=\"(max-width: 150px) 100vw, 150px\" \/><\/td>\n<td><strong>Figure 2: slg+ (1, 3) and clg+ (2, 4) lymphoid cells in adult chicken spleen (1), 3-day embryonic yolk sac (2), I l day embryonic blood (3) and 12-day embryonic bursal <br>mesenchyme (4). <\/strong><p><\/p>\n<p><a href=\"https:\/\/biomedpharmajournal.org\/wp-content\/uploads\/2023\/09\/Vol16No3_Ana_Mas_Fig2.jpg\" target=\"_blank\" rel=\"noopener noreferrer\">Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n<p class=\"wp-block-paragraph\">Daily\nsamples of ten to twenty-one day bursas (fourteen to nineteen at each stage)\nwere taken. Indirect immunofluorescence was used to check for L chain +, IgG +,\nIgM +, and IgA + cells in at least two sections per bursa. Phase contrast was\nused to locate labeled cells, and some of them were moved following Giemsa\nstaining. Tables 1 and 2 provide summaries of the findings.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Table 1: Frequency of lymphoid cells expressing Ig in the 3\u20138-day embryonic yolk sac.<\/strong> <strong>(source: Lebacq, et al 1979)&nbsp;<\/strong><\/p>\n\n\n<table style=\"width: 95%;\" border=\"1\" cellspacing=\"0\" cellpadding=\"4\">\n<tbody>\n<tr>\n<td rowspan=\"2\" width=\"156\">\n<p style=\"text-align: center;\"><strong>Developmental age (days)<\/strong><\/p>\n<\/td>\n<td style=\"text-align: center;\" colspan=\"2\" width=\"312\">\n<p><strong>Ig-containing cells in yolk sac* (%)<\/strong><\/p>\n<\/td>\n<td style=\"text-align: center;\" rowspan=\"2\" width=\"156\">\n<p><strong>Red blood cells in yolk sac (%)<\/strong><\/p>\n<\/td>\n<td style=\"text-align: center;\" rowspan=\"2\" width=\"156\">\n<p><strong>Ig-containing cells in non-red blood cells of yolk sac (%)<\/strong><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"156\">\n<p><strong>DIF<\/strong><\/p>\n<\/td>\n<td width=\"156\">\n<p style=\"text-align: center;\"><strong>IIF<\/strong><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"156\">\n<p style=\"text-align: center;\">3<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"156\">\n<p>NT\u00a7<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"156\">\n<p>0-04<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"156\">\n<p>95<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"156\">\n<p>0-8<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"156\">\n<p>6<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"156\">\n<p>0<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"156\">\n<p>NT<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"156\">\n<p>&nbsp;<\/p>\n<\/td>\n<td width=\"156\">\n<p style=\"text-align: center;\">&nbsp;<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"156\">\n<p>&nbsp;<\/p>\n<\/td>\n<td width=\"156\">\n<p style=\"text-align: center;\">0<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"156\">\n<p>NT<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"156\">\n<p>&nbsp;<\/p>\n<\/td>\n<td width=\"156\">\n<p style=\"text-align: center;\">&nbsp;<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"156\">\n<p>&nbsp;<\/p>\n<\/td>\n<td width=\"156\">\n<p style=\"text-align: center;\">&lt;0-01<\/p>\n<\/td>\n<td width=\"156\">\n<p style=\"text-align: center;\">NT<\/p>\n<\/td>\n<td width=\"156\">\n<p>&nbsp;<\/p>\n<\/td>\n<td width=\"156\">\n<p>&nbsp;<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"156\">\n<p>&nbsp;<\/p>\n<\/td>\n<td width=\"156\">\n<p style=\"text-align: center;\">0-01<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"156\">\n<p>0-02<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"156\">\n<p>87-5<\/p>\n<\/td>\n<td width=\"156\">\n<p style=\"text-align: center;\">0-15<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"156\">\n<p style=\"text-align: center;\">7<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"156\">\n<p>0-03<\/p>\n<\/td>\n<td width=\"156\">\n<p style=\"text-align: center;\">NT<\/p>\n<\/td>\n<td width=\"156\">\n<p>&nbsp;<\/p>\n<\/td>\n<td width=\"156\">\n<p>&nbsp;<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"156\">\n<p>&nbsp;<\/p>\n<\/td>\n<td width=\"156\">\n<p style=\"text-align: center;\">0-02<\/p>\n<\/td>\n<td width=\"156\">\n<p style=\"text-align: center;\">NT<\/p>\n<\/td>\n<td width=\"156\">\n<p>&nbsp;<\/p>\n<\/td>\n<td width=\"156\">\n<p>&nbsp;<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"156\">\n<p>&nbsp;<\/p>\n<\/td>\n<td width=\"156\">\n<p style=\"text-align: center;\">0-02<\/p>\n<\/td>\n<td width=\"156\">\n<p style=\"text-align: center;\">NT<\/p>\n<\/td>\n<td width=\"156\">\n<p>&nbsp;<\/p>\n<\/td>\n<td width=\"156\">\n<p>&nbsp;<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"156\">\n<p>&nbsp;<\/p>\n<\/td>\n<td width=\"156\">\n<p style=\"text-align: center;\">0-03<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"156\">\n<p>0-03<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"156\">\n<p>76<\/p>\n<\/td>\n<td width=\"156\">\n<p style=\"text-align: center;\">0-12<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"156\">\n<p style=\"text-align: center;\">8<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"156\">\n<p>0-02<\/p>\n<\/td>\n<td width=\"156\">\n<p style=\"text-align: center;\">NT<\/p>\n<\/td>\n<td width=\"156\">\n<p>&nbsp;<\/p>\n<\/td>\n<td width=\"156\">\n<p>&nbsp;<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"156\">\n<p style=\"text-align: center;\">&nbsp;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"156\">\n<p>0-01<\/p>\n<\/td>\n<td width=\"156\">\n<p style=\"text-align: center;\">NT<\/p>\n<\/td>\n<td width=\"156\">\n<p>&nbsp;<\/p>\n<\/td>\n<td width=\"156\">\n<p>&nbsp;<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"156\">\n<p>&nbsp;<\/p>\n<\/td>\n<td width=\"156\">\n<p style=\"text-align: center;\">0-02<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"156\">\n<p>0-03<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"156\">\n<p>86<\/p>\n<\/td>\n<td width=\"156\">\n<p style=\"text-align: center;\">0-21<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"156\">\n<p style=\"text-align: center;\">10<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"156\">\n<p>0-03<\/p>\n<\/td>\n<td width=\"156\">\n<p style=\"text-align: center;\">NT<\/p>\n<\/td>\n<td width=\"156\">\n<p>&nbsp;<\/p>\n<\/td>\n<td width=\"156\">\n<p>&nbsp;<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"156\">\n<p>&nbsp;<\/p>\n<\/td>\n<td width=\"156\">\n<p style=\"text-align: center;\">NT<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"156\">\n<p>0-04<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"156\">\n<p>NT<\/p>\n<\/td>\n<td width=\"156\">\n<p style=\"text-align: center;\">NT<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p><strong>&nbsp;<\/strong><\/p>\n\n\n<p class=\"wp-block-paragraph\"><strong>Table 2: Ig+ cells&#8217; emergence, distribution, and frequency during the development of the embryonic bursa (source: Lebacq,et al 1979)<\/strong>.<\/p>\n\n\n<table style=\"width: 95%;\" border=\"1\" cellspacing=\"0\" cellpadding=\"4\">\n<tbody>\n<tr>\n<td rowspan=\"2\" width=\"111\">\n<p style=\"text-align: center;\"><strong>Age of embryo (days)<\/strong><\/p>\n<\/td>\n<td style=\"text-align: center;\" colspan=\"6\" width=\"668\">\n<p><strong>Location of Ig + cells*<\/strong><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"111\">\n<p><strong>Outer M<\/strong><\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p><strong>Inner M<\/strong><\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p><strong>Touching E<\/strong><\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p><strong>Plain E<\/strong><\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p><strong>Thickened E<\/strong><\/p>\n<\/td>\n<td width=\"111\">\n<p style=\"text-align: center;\"><strong>Foll<\/strong><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"111\">\n<p style=\"text-align: center;\">9<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>-+<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&#8211;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&#8211;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&#8211;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&#8211;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&#8211;<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"111\">\n<p>10<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&#8211;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&#8211;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&#8211;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&#8211;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&#8211;<\/p>\n<\/td>\n<td width=\"111\">\n<p style=\"text-align: center;\">&#8211;<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"111\">\n<p style=\"text-align: center;\">11<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>+<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&#8211;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&#8211;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&#8211;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&#8211;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&#8211;<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"111\">\n<p>12<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>+<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>++<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>+<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&#8211;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&#8211;<\/p>\n<\/td>\n<td width=\"111\">\n<p style=\"text-align: center;\">&#8211;<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"111\">\n<p style=\"text-align: center;\">13 early<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&#8211;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>++<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>+<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>+<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>+<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&#8211;<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"111\">\n<p>13 late<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&nbsp;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>+<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>+<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>+<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>+<\/p>\n<\/td>\n<td width=\"111\">\n<p style=\"text-align: center;\">+<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"111\">\n<p style=\"text-align: center;\">14<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&nbsp;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>+<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>+<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&nbsp;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&nbsp;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>++<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"111\">\n<p>16<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&nbsp;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>++<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&nbsp;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&nbsp;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&nbsp;<\/p>\n<\/td>\n<td width=\"111\">\n<p style=\"text-align: center;\">+++<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"111\">\n<p style=\"text-align: center;\">18<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&nbsp;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>++<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&nbsp;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&nbsp;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&nbsp;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>++++<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"111\">\n<p>21<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&nbsp;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>++<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&nbsp;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&nbsp;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"111\">\n<p>&nbsp;<\/p>\n<\/td>\n<td width=\"111\">\n<p style=\"text-align: center;\">+++++<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n<p class=\"wp-block-paragraph\"><strong>Table 3. When, where, and how frequently IgM+, IgA+, and IgG+ cells emerge throughout the development of the embryonic bursa (source: Lebacq,et al 1979)<\/strong>.<\/p>\n\n\n<table style=\"width: 95%;\" border=\"1\" cellspacing=\"0\" cellpadding=\"4\">\n<tbody>\n<tr>\n<td rowspan=\"2\" width=\"130\">\n<p style=\"text-align: center;\">Age of embyro (days)<\/p>\n<\/td>\n<td style=\"text-align: center;\" rowspan=\"2\" width=\"130\">\n<p>Location of Ig + cells<\/p>\n<\/td>\n<td style=\"text-align: center;\" colspan=\"4\" width=\"519\">\n<p>Class of cellular Ig+<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"130\">\n<p>\u00b5<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>\u00fd<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>\u03b1b<\/p>\n<\/td>\n<td width=\"130\">\n<p style=\"text-align: center;\">\u03b1s<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"130\">\n<p style=\"text-align: center;\">11<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>M<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>-\u00b1<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>&#8211;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>&#8211;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>+<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"130\">\n<p>&nbsp;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>E<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>&#8211;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>&#8211;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>&#8211;<\/p>\n<\/td>\n<td width=\"130\">\n<p style=\"text-align: center;\">&#8211;<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"130\">\n<p style=\"text-align: center;\">12<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>M<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>&#8211;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>&#8211;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>&#8211;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>++<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"130\">\n<p>&nbsp;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>E<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>&#8211;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>&#8211;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>&#8211;<\/p>\n<\/td>\n<td width=\"130\">\n<p style=\"text-align: center;\">&#8211;<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"130\">\n<p style=\"text-align: center;\">13<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>M<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>+<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>+<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>+<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>++<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"130\">\n<p>&nbsp;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>E-F<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>+<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>+<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>+<\/p>\n<\/td>\n<td width=\"130\">\n<p style=\"text-align: center;\">+<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"130\">\n<p style=\"text-align: center;\">14<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>M<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>+<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>+<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>+<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>++<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"130\">\n<p>&nbsp;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>F<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>++<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>+<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>+<\/p>\n<\/td>\n<td width=\"130\">\n<p style=\"text-align: center;\">+<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"130\">\n<p style=\"text-align: center;\">16<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>M<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>++<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>+<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>NT<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>++<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"130\">\n<p>&nbsp;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>F<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>+++<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>+<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>NT<\/p>\n<\/td>\n<td width=\"130\">\n<p style=\"text-align: center;\">++<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"130\">\n<p style=\"text-align: center;\">21<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>M<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>++<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>++<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>NT<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>++<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"130\">\n<p>&nbsp;<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>F<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>++++<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>++++<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"130\">\n<p>NT<\/p>\n<\/td>\n<td width=\"130\">\n<p style=\"text-align: center;\">++++<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n<p class=\"wp-block-paragraph\">At day 14, five to ten percent of\nthe follicles had big cIg+ basophilic cells that were vividly labeled by anti-L\nand anti-,u antibodies (Fig. 2). However, sIgM + lymphoid cells were also\ndiscovered outside of the follicles. In follicles and mesenchyme, the anti-y,\nanti-a, and anti-ab reagents labeled sporadic cells (Fig. 3).<\/p>\n\n\n<table style=\"width: 70%;\" border=\"1\" cellpadding=\"5\">\n<tbody>\n<tr>\n<td><img decoding=\"async\" class=\"alignnone size-thumbnail wp-image-51459\" src=\"https:\/\/biomedpharmajournal.org\/wp-content\/uploads\/2023\/09\/Vol16No3_Ana_Mas_Fig3-150x150.jpg\" alt=\"\" width=\"150\" height=\"150\" srcset=\"https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2023\/09\/Vol16No3_Ana_Mas_Fig3-150x150.jpg 150w, https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2023\/09\/Vol16No3_Ana_Mas_Fig3-256x256.jpg 256w, https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2023\/09\/Vol16No3_Ana_Mas_Fig3.jpg 651w\" sizes=\"(max-width: 150px) 100vw, 150px\" \/><\/td>\n<td>\n<p><strong>Figure 3: IgM+ (1, 2) and IgA+ (3, 4) cells in mesenchyme and bursal follicles of 14-day embryos (2, 4). indirect immunofluorescence on tissue slices with wax embedding.<\/strong><\/p>\n<p><\/p>\n<p><a href=\"https:\/\/biomedpharmajournal.org\/wp-content\/uploads\/2023\/09\/Vol16No3_Ana_Mas_Fig3.jpg\" target=\"_blank\" rel=\"noopener noreferrer\">Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n<p class=\"wp-block-paragraph\"><strong>Discussion<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Ontogeny,\nB-cell precursors, chicken embryos, and incubation were the search terms used\nto find 15350 articles in the databases of PubMed, NCBI, and Google Scholar.\nAfter a second round of selection based on the inclusion and exclusion\ncriteria, 38 articles that met the inclusion criteria were retrieved.\nThe\nstudy described here was designed to investigate the potential for extra-bursal\nB-cell development in the early avian embryo. Using purified antibodies to\nchicken Ig chains in a sensitive indirect immunofluorescence assay on fixed\ncell smears and wax-embedded tissue sections, we were able to identify in 3 day\nand older embryonic yolk sac, 11 and 12 day blood, and 11, 12 and 13 day bursal\nmesenchyme a limited population of putative B-cell precursors characterized by\nthe presence of small amounts of cytoplasmic Ig and a lymphoid morphology. No\nearly chicken embryos without clg lymphoid cells are known to exist at this\ntime. As a result, the earliest sIgA and sIgM cells were found in the yolk sac\non day 5, the bursa and spleen on day 10, and the follicles of the Fabricius\nembryonic bursa on day 14<sup>8<\/sup>.\nIncubation began in 1976.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The following technical factors were\ncrucial for identifying the weakly labelled cIg lymphoid cells in the chicken\nembryo: (1) the specificity of the anti-Ig reagents; (2) the affinity of the\nanti-Ig reagents, which allowed their use at 15 ug\/ml and made the labeling by\nunidentified contaminating antibodies extremely unlikely; (3) the sensitivity\nof the assay, which allowed the detection of minute amounts of labelled Igs;\nand (4) the. Identifying whether the intracellular Ig in the early clg yolk sac\ncells came from the mother or the embryo is crucial. Considering that the yolk\ncontains a significant amount of maternal IgG<sup>13<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Albumin contains very small amounts\nof IgM and IgA<sup>14<\/sup>.\nAlthough the vitelline membrane and eventually an extension of the chorion\ncontinue to separate the yolk and albumin, it is unlikely that these\nmacromolecules will contaminate early yolk sac cells<sup>15<\/sup>.\nLarge lymphoid cells with IgM or possibly IgA were found in the early yolk sac\n(3 days of incubation and onward). The remaining labelled material was made up\nof yolk spheres, vacuolated macrophage-like cells, and entodermal cells\ncontaining IgG. The Ig in the clg lymphoid cells, in contrast to these, was\nuniformly distributed throughout the cytoplasm, making it unlikely that it was\nobtained extrinsically through pinocytosis. To formally prove that IgM and\npossibly IgA in early yolk sac cells have embryonic origins, allotypic markers\nwould be required.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Large pre-B cells described in murine\nare similar to the large cIgM cells found in the yolk sac of a three-day-old\nmouse<sup>16<\/sup>.\nIn general, membrane-bound IgM<sup>7<\/sup> the\nvalidity of which is currently under investigation. Since the primordium of the\nbursa has not yet begun to form on day three of incubation, it can be formally\nexcluded<sup>17<\/sup>.\nThe size of the small pre-B cells found in the blood, lymph nodes, liver, and\nspleen of human fetuses is comparable to that of the small clg lymphoid cells\nfound in I1 to 13 day bursal mesenchyme<sup>6<\/sup>.\nSimilar to human development, they were examined at later stages while being\nstained. Interesting studies using anti-H chain reagents showed that the\nmajority of these cIg lymphoid cells, indicating the existence of a second\nantibody specificity in the former reagent. The two other reagents that were\nsaid to have labeled the earliest sIg cells found in the yolk sac, thymus, and\nbursa of chicken embryos may also have fit into this category<sup>18<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Our antibody preparations were\nidentical in immunoelectrophoresis and indirect immunofluorescence on adult\nchicken spleen and jejunum sections<sup>19<\/sup> with\nthe exception of when tested on embryonic bursa sections. The reagent obviously\nneeds to be studied further in order to fully understand this additional\nspecificity. What relationships exist between the clg large lymphoid cells of the\nearly yolk sac (days 3), blood (days 11 and 12), bursal follicles (day 14), and\nthe temporally intermediate cIg small lymphoid cells of bursal mesenchyme (day\n11) Over time, the circumstances surrounding what occurs to Ig cells in the\nembryonic bursa become more complicated. Starting on day 14 of incubation,\nsmall numbers of cIgA and cIgG cells were present in the bursal follicles in\naddition to the large basophilic cIgM cells.Lawton et al. states the following, the percentage of bursa cells\nthat switch IgM biosynthesis to IgA or IgG biosynthesis<sup>10<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The\nwidely held dogma states that the generation of B cells with a highly diverse\nreceptor repertoire occurs in the bone marrow continuously throughout a\nperson&#8217;s life. This is unquestionably true for humans and mice, but many higher\nvertebrate species use a different approach, which incorporates gut-associated\nlymphoid tissue (GALT) structures, to broaden the B cell repertoire. The\nchicken, which has the bursa of Fabricius as its principal B cell organ, is the\nbest illustration of this option. Pre-bursal, bursal, and post-bursal phases\nare the three separate phases of B cell development in chickens. Hematopoietic\nprecursor cells, which come from para-aortic foci of intra-embryonic\nmesenchyme, commit to the B cell lineage during the pre-bursal phase and move\nthrough the blood to numerous lymphoid organs like the spleen and bone marrow.\nThe bursal phase begins between embryonic days 9 (ED9) and 12 (ED12), when a\nlimited number of pre-bursal stem cells go to the bursa anlage, where only 2\u20135\nB cell precursors colonize each of the 10,000\u201312,000 lymphoid follicles. The\nproliferative expansion of cells takes place inside the follicles. B cells must\nproduce a wide range of distinct B cell receptors (BCRs) in order to recognize\nthe enormous number of potential antigens. As a result, starting around ED15,\nthe bursal environment causes gene conversion, rather than gene rearrangement,\nas it does in humans and mice, to cause the BCR to diversify. Around hatch, the\npost-bursal phase starts, and it lasts until bursa involution. When exposed to\nantigen, immature bursal B cells with functioning and diverse BCR begin to\nmigrate to the periphery and spread to the secondary lymphoid organs, where\nthey can develop into cells that secrete antibodies. The percentage of\nmigratory cells is incredibly modest, and more than 90% of bursal B-cells\nundergo apoptosis before dying. After hatching, the formerly homogeneous bursa\nfollicles separate into a dense, highly growing B-cell cortex and a more\nheterogeneous medulla comprising B-cells, a variety of myeloid cells, and\nstroma cells, including bursal secretory dendritic cells. Highly specialized sequential\ncell migration procedures are required to produce initially proliferative and\nthen compartmentalized B cell follicles in the bursa and to seed peripheral\nlymphatic systems with B cells from the bursa. B cell precursors must initially\nmigrate into the bursal anlage&#8217;s mesenchyme in the first stage of their\nmigration. Those first bursal B cells must then move from the bursal mesenchyme\ninto forming follicular buds during a second migration stage. These bursal\nsecretory dendritic cells (BSDC), which are of hematopoietic origin and cross\nthe basement membrane under the surface epithelium to generate a so-called\ndendro-epithelial tissue, are what cause the formation of these follicular\nbuds. B cells move to the follicular border in a third migratory stage as the\nonce homogeneous follicles divide into cortex and medulla. As a result, close\nto hatch, some B cells cross the line and move into a layer of mesenchymal\nreticular cells that are desmin and vimentin positive, where they continue to\nmultiply. A tiny percentage of B cells finally emigrate in a fourth migration\nstep, mostly from the follicular cortex of the bursa to the peripheral lymphoid\norgans <sup>23-30<\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Conclusion<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">After 15350 items were discovered\nusing keyword searches in the PubMed, NCBI, and Google Scholar databases, 38\npapers met the criteria for inclusion. According to the study&#8217;s findings, the\nembryonic bursa of Fabricius appears to receive two different types of migrant\ncells: clglarge basophilic hemopoietic stem cells and cIg small lymphoid B-cell\nprecursors. Therefore, the bursa of Fabricius is not the only location where B\nlymphopoiesis occurs in the avian embryo. Although the yolk sac and the\nhaemopoietic tissues surrounding the dorsal aorta are strong candidates, the\nidentity of the extra-bursal site is unknown. Thus, general haemopoietic tissues\nmay serve as the initial site of B lymphopoiesis in both birds and mammals.\nOnly later in the course of avian development do the bursal follicles become\naccessible and take over.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Funding Statement <\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">There is no funding for this research\/text. Everything\nis done personally by the author.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>References<\/strong><\/p>\n\n\n\n<ol class=\"wp-block-list\"><li>Nossal GJ V, Pike BL. Differentiation of B lymphocytes from stem cell precursors. 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A possible homologue of mammalian IgA in chicken serum and secretions. <em>Immunology<\/em>. 1972;22(1):165.<\/li><\/ol>\n","protected":false},"excerpt":{"rendered":"<p>Introduction In mammals1 birds 2,3 and avian embryos, lymphoid cells  [&#8230;]<\/p>\n","protected":false},"author":15,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[109],"tags":[],"class_list":["post-51436","post","type-post","status-publish","format-standard","hentry","category-vol16no3"],"_links":{"self":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/51436","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/users\/15"}],"replies":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/comments?post=51436"}],"version-history":[{"count":5,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/51436\/revisions"}],"predecessor-version":[{"id":52559,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/51436\/revisions\/52559"}],"wp:attachment":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/media?parent=51436"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/categories?post=51436"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/tags?post=51436"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}