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Open Access

IL-21 and BAFF/BLyS synergize in stimulating plasma cell differentiation from human marginal zone B cells as well as from circulating peripheral blood B cells from autoimmune patients

  • Rachel Ettinger1,
  • Stefan Kuchen1,
  • Gary P Sims1,
  • Rachel Robbins1,
  • David Withers1,
  • Randy T Fischer1 and
  • Peter E Lipsky1
Arthritis Research & Therapy20079(Suppl 3):P8

Published: 19 October 2007


Public HealthRheumatoid ArthritisArthritisSystemic Lupus ErythematosusCell Differentiation

IL-21 promotes plasma cell (PC) differentiation while BAFF promotes B-cell survival. Here, we report that IL-21 synergizes with BAFF to elicit BLIMP-1 induction, PC differentiation and IgG production from a novel population of human splenic memory B cells. These human marginal zone analogue B cells are exquisitely sensitive to IL-21 and BAFF in the absence of further co-stimulation. The ability of IgG+ marginal zone analogue to respond specifically and exclusively to IL-21 and BAFF demonstrates that they are uniquely poised to respond to antigen-independent signals and differentiate into IgG-producing PC, thereby replenishing serologic memory. Importantly, peripheral blood B cells from a portion of patients with systemic lupus erythematosus and rheumatoid arthritis were highly responsive to stimulation with IL-21 and BAFF. These data suggest that IL-21 and BAFF may be capable of inducing PC differentiation from memory B cells with autoreactive specificities and thereby contribute to autoimmunity.

Authors’ Affiliations

Autoimmunity Branch, NIAMS, National Institutes of Health, Bethesda, USA


© BioMed Central Ltd 2007