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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,7,21]]},"abstract":"<jats:p>\n                    The bursa of Fabricius (BF), a specialized lymphoid structure in birds, regulates avian B-cell development. However, the BF starts to regress posthatching, suggesting that as-yet-unidentified structures assume this function during maturation. This study reveals that BF-independent B-cell genesis involving the gut cecal tonsils (CTs) predominates over the BF-dependent pathway posthatching. Although B-cell progenitors originating from the bone marrow (BM) typically migrate to the BF, we identified a population that instead migrates to the CTs through CXCL12\/CXCR4-mediated chemotaxis. These BF-independent CXCR4\n                    <jats:sup>+<\/jats:sup>\n                    pre-B cells acquired surface IgM expression within the CT follicular region (FR) and differentiated into immunoglobulin A (IgA)-producing plasma cells. Inhibition of CXCR4\n                    <jats:sup>+<\/jats:sup>\n                    cell influx from the BM impaired formation of the FR, altered the responsiveness of intestinal IgA to commensal bacteria, promoted gut dysbiosis, allowed translocation of pathogenic bacteria (e.g.,\n                    <jats:italic toggle=\"yes\">Streptococcus alactolyticus<\/jats:italic>\n                    ) to the liver, and ultimately caused hepatic inflammation and metabolic dysfunction. These abnormalities were reversed by administering an IgA-enriched fecal preparation derived from healthy chickens. Collectively, these results reveal the existence of a population of BF-independent B cells that function in CTs. These cells represent a promising target for maintaining and improving the immunological and microbiological environment of the avian intestinal tract, which is closely linked to hepatic homeostasis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2605569123","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T16:19:51Z","timestamp":1784132391000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["Bursa of Fabricius\u2013independent B cells establish an IgA-mediated intestinal barrier that safeguards gut\u2013liver homeostasis"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0302-2851","authenticated-orcid":false,"given":"Ryota","family":"Hirakawa","sequence":"first","affiliation":[{"name":"International Education and Research Center for Food and Agricultural Immunology, Graduate School of Agricultural Science, Tohoku 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Hirakawa 16S rRNA amplicon sequence data-1 (Surgical treatment study) from \u201cBursa of Fabricius\u2013independent B cells establish an IgA-mediated intestinal barrier that safeguards gut\u2013liver homeostasis.\u201d NCBI Biopreoject. https:\/\/www.ncbi.nlm.nih.gov\/bioproject\/PRJNA1346295. Deposited 26 June 2026."},{"key":"e_1_3_4_41_2","unstructured":"R. Hirakawa 16S rRNA amplicon sequence data-2 (Fecal material transfer study) from \u201cBursa of Fabricius\u2013independent B cells establish an IgA-mediated intestinal barrier that safeguards gut\u2013liver homeostasis.\u201d NCBI Biopreoject. https:\/\/www.ncbi.nlm.nih.gov\/bioproject\/PRJNA1346473. Deposited 26 June 2026."},{"key":"e_1_3_4_42_2","unstructured":"R. Hirakawa Bulk RNA-seq data from \u201cBursa of Fabricius\u2013independent B cells establish an IgA-mediated intestinal barrier that safeguards gut\u2013liver homeostasis.\u201d NCBI Biopreoject. https:\/\/www.ncbi.nlm.nih.gov\/bioproject\/PRJNA1346141. 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