IL-27 supports germinal center function by enhancing IL-21 production and the function of T follicular helper cells
Maturation and selection of high-affinity B cell clones in the germinal center (GC) relies on support from T follicular helper (T(FH)) cells. T(FH) cells are characterized by their localization to the B cell follicle and their high expression of the costimulatory molecules ICOS and PD1 and the cytokine IL-21, which promotes immunoglobulin (Ig) class switching and production by B cells. We show that the heterodimeric cytokine IL-27 is critical for the function of T(FH) cells and for normal and pathogenic GC responses. IL-27 signaling to T cells results in the production of IL-21, a known autocrine factor for the maintenance of T(FH) cells, in a STAT3-dependent manner. IL-27 also enhances the survival of activated CD4(+) T cells and the expression of T(FH) cell phenotypic markers. In vivo, expression of the IL-27Ralpha chain is required to support IL-21 production and T(FH) cell survival in a T cell-intrinsic manner. The production of high-affinity antibodies is reduced, and pristane-elicited autoantibodies and glomerulonephritis are significantly diminished, in Il27ra(-/-) mice. Together, our data show a nonredundant role for IL-27 in the development of T cell-dependent antibody responses.
|ISBN||0022-1007 (Linking) 0022-1007 (Linking)|
|Authors||Batten, M.; Ramamoorthi, N.; Kljavin, N. M.; Ma, C. S.; Cox, J. H.; Dengler, H. S.; Danilenko, D. M.; Caplazi, P.; Wong, M.; Fulcher, D. A.; Cook, M. C.; King, C.; Tangye, S. G.; de Sauvage, F. J.; Ghilardi, N.:|
|Publisher Name||JOURNAL OF EXPERIMENTAL MEDICINE|
|DOI||jem.20100064 [pii] 10.1084/jem.20100064|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21098093|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/10530|