title: IL-21 and BAFF/BLyS synergize in stimulating plasma cell differentiation from a unique population of human splenic memory B cells.
abstract: Both constitutive Ig secretion by long-lived plasma cells (PC) and the recurrent differentiation of memory (mem) B cells into PC contribute to the maintenance of serologic mem. However, the relative contribution of each is unknown. 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.
authors.affiliation: Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA. ettingerr@mail.nih.gov
authors.forename: Rachel
authors.initials: R
authors.lastname: Ettinger
authors.forename: Gary P
authors.initials: GP
authors.lastname: Sims
authors.forename: Rachel
authors.initials: R
authors.lastname: Robbins
authors.forename: David
authors.initials: D
authors.lastname: Withers
authors.forename: Randy T
authors.initials: RT
authors.lastname: Fischer
authors.forename: Amrie C
authors.initials: AC
authors.lastname: Grammer
authors.forename: Stefan
authors.initials: S
authors.lastname: Kuchen
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lipsky
mesh_terms: D000941:Antigens / Q000276:immunology; D053264:B-Cell Activating Factor / Q000819:agonists* / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007156:Immunologic Memory; D007378:Interleukins / Q000819:agonists* / Q000276:immunology; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D014157:Transcription Factors / Q000276:immunology; D000098546:Interleukin-21
chemical_list: D000941:Antigens; D053264:B-Cell Activating Factor; D019013:CD40 Antigens; D007074:Immunoglobulin G; D007378:Interleukins; D012097:Repressor Proteins; D014157:Transcription Factors; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1; D000098546:Interleukin-21