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In this study, we describe a novel population of human postswitched mem B cells that rapidly differentiate into PC and thus contribute to serologic mem. These IgG+ B cells reside in the region of human spleen analogous to the murine marginal zone and have not previously been examined. These cells are highly responsive to IL-21 in the context of CD40 stimulation. Uniquely, IgG+ marginal zone analog B cells are exquisitely sensitive to the combination of IL-21 and B cell-activating factor belonging to the TNF family (BAFF\/BLyS) that synergize in the absence of further costimulation to induce up-regulation of B lymphocyte-induced maturation protein-1 and drive PC differentiation. Other cytokine combinations are not active in this regard. This is the first demonstration that this unique population of mem B cells can respond specifically and exclusively to IL-21 and BAFF\/BLyS by differentiating into IgG-secreting PC, and thus contributing to serologic mem in an Ag-independent manner.<\/jats:p>","DOI":"10.4049\/jimmunol.178.5.2872","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T13:14:39Z","timestamp":1397826879000},"page":"2872-2882","source":"Crossref","is-referenced-by-count":138,"title":["IL-21 and BAFF\/BLyS Synergize in Stimulating Plasma Cell Differentiation from a Unique Population of Human Splenic Memory B Cells"],"prefix":"10.1093","volume":"178","author":[{"given":"Rachel","family":"Ettinger","sequence":"first","affiliation":[{"name":"Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary P","family":"Sims","sequence":"additional","affiliation":[{"name":"Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Robbins","sequence":"additional","affiliation":[{"name":"Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Withers","sequence":"additional","affiliation":[{"name":"Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randy T","family":"Fischer","sequence":"additional","affiliation":[{"name":"Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amrie C","family":"Grammer","sequence":"additional","affiliation":[{"name":"Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kuchen","sequence":"additional","affiliation":[{"name":"Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter E","family":"Lipsky","sequence":"additional","affiliation":[{"name":"Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,3,1]]},"reference":[{"key":"2026012810514996700_R1","first-page":"303","volume-title":"Immunol. 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