IL-21 Induces Differentiation of Human Naive and Memory B Cells into Antibody-Secreting Plasma Cells

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  • Rachel Ettinger
    *Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases and
  • Gary P. Sims
    *Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases and
  • Anna-Marie Fairhurst
    *Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases and
  • Rachel Robbins
    *Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases and
  • Yong Sing da Silva
    *Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases and
  • Rosanne Spolski
    †Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892
  • Warren J. Leonard
    †Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892
  • Peter E. Lipsky
    *Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases and

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<jats:title>Abstract</jats:title><jats:p>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.</jats:p>

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