期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 207, 期 13, 页码 2895-2906出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20100064
关键词
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资金
- Australian National Health and Medical Research Council
- Cancer Institute of New South Wales
- Juvenile Diabetes Research Foundation
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-27R alpha 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 II27ra(-/-) mice. Together, our data show a nonredundant role for IL-27 in the development of T cell-dependent antibody responses.
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