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

Michelle A Linterman, Laura Beaton, Di Yu, Roybel R Ramiscal, Monika Srivastava, Jennifer J Hogan, Naresh K Verma, Mark J Smyth, Robert J Rigby, Carola Vinuesa

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532 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)353 - 363
Number of pages11
JournalJournal of Experimental Medicine
Volume207
Issue number2
DOIs
Publication statusPublished - 2010
Externally publishedYes

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