IL-21 induces differentiation of human naive and memory B cells into antibody-secreting plasma cells.
IL-21 is a type I cytokine that influences the function of T cells, NK cells, and B cells. In this study, we report that IL-21 plays a major role in stimulating the differentiation of human B cells. When human B cells were stimulated through the BCR, IL-21 induced minimal proliferation, IgD down-modulation, and small numbers of plasma cells. In contrast, after CD40 engagement, IL-21 induced extensive proliferation, class switch recombination (CSR), and plasma cell differentiation. Upon cross-linking both BCR and CD40, IL-21 induced the largest numbers of plasma cells. IL-21 drove both postswitch memory cells as well as poorly responsive naive cord blood B cells to differentiate into plasma cells. The effect of IL-21 was more potent than the combination of IL-2 and IL-10, especially when responsiveness of cord blood B cells was examined. IL-21 costimulation potently induced the expression of both B lymphocyte-induced maturation protein-1 (BLIMP-1) and activation-induced cytidine deaminase as well as the production of large amounts of IgG from B cells. Despite the induction of activation-induced cytidine deaminase and CSR, IL-21 did not induce somatic hypermutation. Finally, IL-2 enhanced the effects of IL-21, whereas IL-4 inhibited IL-21-induced plasma cell differentiation. Taken together, our data show that IL-21 plays a central role in CSR and plasma cell differentiation during T cell-dependent B cell responses.
Ettinger
Rachel
R
Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892, USA. ettingerr@mail.nih.gov
Sims
Gary P
GP
Fairhurst
Anna-Marie
AM
Robbins
Rachel
R
da Silva
Yong Sing
YS
Spolski
Rosanne
R
Leonard
Warren J
WJ
Lipsky
Peter E
PE
D000917:Antibody Formation / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D019013:CD40 Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation; D006801:Humans; D017578:Immunoglobulin Class Switching; D007156:Immunologic Memory; D007378:Interleukins / Q000494:pharmacology*; D010950:Plasma Cells / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D000098546:Interleukin-21
D019013:CD40 Antigens; D007378:Interleukins; D011947:Receptors, Antigen, B-Cell; D000098546:Interleukin-21