{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:10:00Z","timestamp":1779149400466,"version":"3.51.4"},"reference-count":61,"publisher":"American Society for Clinical Investigation","issue":"19","license":[{"start":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T00:00:00Z","timestamp":1633651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["91942302,31870898,81811540035,82011540008"],"award-info":[{"award-number":["91942302,31870898,81811540035,82011540008"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Key R & D Plan of the Ministry of Science and Technology","award":["2019YFE0100600"],"award-info":[{"award-number":["2019YFE0100600"]}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["91942302,2019YFE0100600,31870898,81811540035,82011540008"],"award-info":[{"award-number":["91942302,2019YFE0100600,31870898,81811540035,82011540008"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,8]]},"abstract":"<jats:p>\n                    Hypomorphic\n                    <jats:italic>RAG1<\/jats:italic>\n                    or\n                    <jats:italic>RAG2<\/jats:italic>\n                    mutations cause primary immunodeficiencies and can lead to autoimmunity, but the underlying mechanisms are elusive. We report here a patient carrying a c.116+2T&gt;G homozygous splice site mutation in the first intron of\n                    <jats:italic>RAG1<\/jats:italic>\n                    , which led to aberrant splicing and greatly reduced RAG1 protein expression. B cell development was blocked at both the pro-B to pre-B transition and the pre-B to immature B cell differentiation step. The patient B cells had reduced B cell receptor repertoire diversity and decreased complementarity determining region 3 lengths. Despite B cell lymphopenia, the patient had abundant plasma cells in the BM and produced large quantities of IgM and IgG Abs, including autoantibodies. The proportion of naive B cells was reduced while the frequency of IgD\n                    <jats:sup>\u2013<\/jats:sup>\n                    CD27\n                    <jats:sup>\u2013<\/jats:sup>\n                    double-negative (DN) B cells, which quickly differentiated into Ab-secreting plasma cells upon stimulation, was greatly increased. Immune phenotype analysis of 52 patients with primary immunodeficiency revealed a strong association of the increased proportion of DN B and memory B cells with decreased number and proportion of naive B cells. These results suggest that the lymphopenic environment triggered naive B cell differentiation into DN B and memory B cells, leading to increased Ab production.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.148887","type":"journal-article","created":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T14:02:20Z","timestamp":1633615340000},"source":"Crossref","is-referenced-by-count":15,"title":["RAG1 splicing mutation causes enhanced B cell differentiation and autoantibody production"],"prefix":"10.1172","volume":"6","author":[{"given":"Qing","family":"Min","sequence":"first","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, 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