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

MA Linterman, L Beaton, D Yu, RR Ramiscal… - Journal of Experimental …, 2010 - rupress.org
MA Linterman, L Beaton, D Yu, RR Ramiscal, M Srivastava, JJ Hogan, NK Verma, MJ Smyth
Journal of Experimental Medicine, 2010rupress.org
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 …
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.
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