IL-21 induces differentiation of human naive and memory B cells into antibody-secreting plasma cells

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. The Journal of Immunology, 2005, 176: 7867–7879. I nterleukin-21 is a type I cytokine that signals through a re-ceptor composing of the IL-21R and the common cytokinereceptor -chain (C)3 (1–5). In humans, IL-21 has been shown to be produced by activated peripheral T cells, as well as spontaneously by CXCR5 follicular helper T cells (2, 6). The IL-21R is closely related to the IL-2R -chain and is expressed b