{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T10:56:09Z","timestamp":1782730569936,"version":"3.54.5"},"reference-count":77,"publisher":"Rockefeller University Press","issue":"7","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,7,5]]},"abstract":"<jats:p>The contribution of B cells to the pathology of Omenn syndrome and leaky severe combined immunodeficiency (SCID) has not been previously investigated. We have studied a mut\/mut mouse model of leaky SCID with a homozygous Rag1 S723C mutation that impairs, but does not abrogate, V(D)J recombination activity. In spite of a severe block at the pro\u2013B cell stage and profound B cell lymphopenia, significant serum levels of immunoglobulin (Ig) G, IgM, IgA, and IgE and a high proportion of Ig-secreting cells were detected in mut\/mut mice. Antibody responses to trinitrophenyl (TNP)-Ficoll and production of high-affinity antibodies to TNP\u2013keyhole limpet hemocyanin were severely impaired, even after adoptive transfer of wild-type CD4+ T cells. Mut\/mut mice produced high amounts of low-affinity self-reactive antibodies and showed significant lymphocytic infiltrates in peripheral tissues. Autoantibody production was associated with impaired receptor editing and increased serum B cell\u2013activating factor (BAFF) concentrations. Autoantibodies and elevated BAFF levels were also identified in patients with Omenn syndrome and leaky SCID as a result of hypomorphic RAG mutations. These data indicate that the stochastic generation of an autoreactive B cell repertoire, which is associated with defects in central and peripheral checkpoints of B cell tolerance, is an important, previously unrecognized, aspect of immunodeficiencies associated with hypomorphic RAG mutations.<\/jats:p>","DOI":"10.1084\/jem.20091927","type":"journal-article","created":{"date-parts":[[2010,6,15]],"date-time":"2010-06-15T00:12:34Z","timestamp":1276560754000},"page":"1541-1554","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":91,"title":["Expansion of immunoglobulin-secreting cells and defects in B cell tolerance in\n                    <i>Rag<\/i>\n                    -dependent immunodeficiency"],"prefix":"10.1084","volume":"207","author":[{"given":"Jolan E.","family":"Walter","sequence":"first","affiliation":[{"name":"Division of Immunology and The Manton Center for Orphan Disease Research, Children\u2019s Hospital 1 , 2 , 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