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IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses


During T cell-dependent responses, B cells can either differentiate extrafollicularly into short-lived plasma cells or enter follicles to form germinal centers (GCs). Interactions with T follicular helper (Tfh) cells are required for GC formation and for selection of somatically mutated GC B cells. Interleukin (IL)-21 has been reported to play a role in Tfh cell formation and in B cell growth, survival, and isotype switching. To date, it is unclear whether the effect of IL-21 on GC formation is predominantly a consequence of this cytokine acting directly on the Tfh cells or if IL-21 directly influences GC B cells. We show that IL-21 acts in a B cell-intrinsic fashion to control GC B cell formation. Mixed bone marrow chimeras identified a significant B cell-autonomous effect of IL-21 receptor (R) signaling throughout all stages of the GC response. IL-21 deficiency profoundly impaired affinity maturation and reduced the proportion of IgG1(+) GC B cells but did not affect formation of early memory B cells. IL-21R was required on GC B cells for maximal expression of Bcl-6. In contrast to the requirement for IL-21 in the follicular response to sheep red blood cells, a purely extrafollicular antibody response to Salmonella dominated by IgG2a was intact in the absence of IL-21.

Type Journal
ISBN 1540-9538 (Electronic) 0022-1007 (Linking)
Authors Linterman, M. A.; Beaton, L.; Yu, D.; Ramiscal, R. R.; Srivastava, M.; Hogan, J. J.; Verma, N. K.; Smyth, M. J.; Rigby, R. J.; Vinuesa, C. G.;
Publisher Name J EXP MED
Published Date 2010-01-01 00:00:00
Published Volume 207
Published Issue 2
Published Pages 353-63
Status Published In-print
OpenAccess Link Linterman JEM 353.pdf