{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:03:04Z","timestamp":1791349384692,"version":"4.3.1"},"reference-count":103,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2009,9,1]],"date-time":"2009-09-01T00:00:00Z","timestamp":1251763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Somatic hypermutation normally occurs as a consequence of the expression of activation-induced cytidine deaminase (AID) by Ag-activated, mature B cells during T cell-dependent germinal center responses. Nonetheless, despite their inability to express CD154 and initiate GC responses, patients with type 1 hyper-IgM syndrome (HIGM1) support populations of IgM+IgD+CD27+ B cells that express mutated Ig genes. The origin of these mutated B cells is unknown; the IgM+IgD+CD27+ cells do not express AID and appear to acquire mutations independent of stringent selection by Ag. Here, we demonstrate that immature\/transitional 1 B cells from the bone marrow of CD154-deficient mice express AID and acquire Ig mutations that lack the hallmarks of antigenic selection via BCR signaling. Comparable levels of AID expression was found in developmentally immature B cells recovered from murine fetal liver and from human immature\/transitional 1 B cells recovered from umbilical cord blood. AID expression in human fetal liver was also robust, approaching that of human tonsil tissue and the human germinal center B cell line, Ramos. These observations led us to conclude that AID expression in developing human B cells is the origin of the mutated IgM+IgD+CD27+ B cells present in HIGM1 patients, and we propose that both mice and humans share a latent, AID-dependent pathway for the preimmune diversification of B lymphocytes that is more prominent in chicken, sheep, and rabbits.<\/jats:p>","DOI":"10.4049\/jimmunol.0901548","type":"journal-article","created":{"date-parts":[[2009,8,10]],"date-time":"2009-08-10T21:06:32Z","timestamp":1249938392000},"page":"3237-3248","source":"Crossref","is-referenced-by-count":49,"title":["Activation-Induced Cytidine Deaminase Expression and Activity in the Absence of Germinal Centers: Insights into Hyper-IgM Syndrome"],"prefix":"10.1093","volume":"183","author":[{"given":"Masayuki","family":"Kuraoka","sequence":"first","affiliation":[{"name":"Department of Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiyong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sallie D","family":"Allgood","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University , Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc C","family":"Levesque","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University , Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garnett","family":"Kelsoe","sequence":"additional","affiliation":[{"name":"Department of Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,9,1]]},"reference":[{"key":"2026012811270867700_R1","first-page":"389","article-title":"Intraclonal generation of antibody mutants in germinal centres.","volume-title":"Nature","year":"1991"},{"key":"2026012811270867700_R2","first-page":"1121","article-title":"Maturation of the immune response in germinal centers.","volume-title":"Cell","year":"1991"},{"key":"2026012811270867700_R3","first-page":"18470","article-title":"Specific expression of activation-induced cytidine deaminase (AID), a novel member of the RNA-editing deaminase family in germinal center B cells.","volume-title":"J. 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