{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T05:38:57Z","timestamp":1792733937874,"version":"4.5.0"},"reference-count":62,"publisher":"Rockefeller University Press","issue":"3","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,3,19]]},"abstract":"<jats:p>The contribution of proliferation to B lymphocyte homeostasis and antigen responses is largely unknown. We quantified the replication history of mouse and human B lymphocyte subsets by calculating the ratio between genomic coding joints and signal joints on kappa-deleting recombination excision circles (KREC) of the IGK-deleting rearrangement. This approach was validated with in vitro proliferation studies. We demonstrate that naive mature B lymphocytes, but not transitional B lymphocytes, undergo in vivo homeostatic proliferation in the absence of somatic mutations in the periphery. T cell\u2013dependent B cell proliferation was substantially higher and showed higher frequencies of somatic hypermutation than T cell\u2013independent responses, fitting with the robustness and high affinity of T cell\u2013dependent antibody responses. More extensive proliferation and somatic hypermutation in antigen-experienced B lymphocytes from human adults compared to children indicated consecutive responses upon additional antigen exposures. Our combined observations unravel the contribution of proliferation to both B lymphocyte homeostasis and antigen-induced B cell expansion. We propose an important role for both processes in humoral immunity. These new insights will support the understanding of peripheral B cell regeneration after hematopoietic stem cell transplantation or B cell\u2013directed antibody therapy, and the identification of defects in homeostatic or antigen-induced B cell proliferation in patients with common variable immunodeficiency or another antibody deficiency.<\/jats:p>","DOI":"10.1084\/jem.20060964","type":"journal-article","created":{"date-parts":[[2007,2,20]],"date-time":"2007-02-20T23:23:33Z","timestamp":1172013813000},"page":"645-655","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":266,"title":["Replication history of B lymphocytes reveals homeostatic proliferation and extensive antigen-induced B cell expansion"],"prefix":"10.1084","volume":"204","author":[{"given":"Menno C.","family":"van Zelm","sequence":"first","affiliation":[{"name":"1Erasmus MC, Department of Immunology"},{"name":"2Department of Pediatrics, 3015 GE Rotterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Szczepan\u0301ski","sequence":"additional","affiliation":[{"name":"1Erasmus MC, Department of Immunology"},{"name":"3Department of Pediatric Hematology and Oncology, Silesian Medical Academy, 41-800 Zabrze, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam","family":"van der Burg","sequence":"additional","affiliation":[{"name":"1Erasmus MC, Department of Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques J.M.","family":"van Dongen","sequence":"additional","affiliation":[{"name":"1Erasmus MC, Department of Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2007,2,20]]},"reference":[{"key":"2023072515561521100_BIB1","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/S0167-5699(98)01330-9","volume":"19","year":"1998","journal-title":"Immunol. 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