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.
|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||JOURNAL OF EXPERIMENTAL MEDICINE|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20142429|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/10584|