Follicular Helper NKT Cells Induce Limited B Cell Responses and Germinal Center Formation in the Absence of CD4+ T Cell Help
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AbstractB cells require MHC class II (MHC II)-restricted cognate help and CD40 engagement by CD4+ T follicular helper (TFH) cells to form germinal centers and long-lasting Ab responses. Invariant NKT (iNKT) cells are innate-like lymphocytes that jumpstart the adaptive immune response when activated by the CD1d-restricted lipid α-galactosylceramide (αGalCer). We previously observed that immunization of mice lacking CD4+ T cells (MHC II−/−) elicits specific IgG responses only when protein Ags are mixed with αGalCer. In this study, we investigated the mechanisms underpinning this observation. We find that induction of Ag-specific Ab responses in MHC II−/− mice upon immunization with protein Ags mixed with αGalCer requires CD1d expression and CD40 engagement on B cells, suggesting that iNKT cells provide CD1d-restricted cognate help for B cells. Remarkably, splenic iNKT cells from immunized MHC II−/− mice display a typical CXCR5hiprogrammed death-1hiICOShiBcl-6hi TFH phenotype and induce germinal centers. The specific IgG response induced in MHC II−/− mice has shorter duration than that developing in CD4-competent animals, suggesting that iNKTFH cells preferentially induce transient rather than long-lived Ab responses. Together, these results suggest that iNKT cells can be co-opted into the follicular helper function, yet iNKTFH and CD4+ TFH cells display distinct helper features, consistent with the notion that these two cell subsets play nonredundant functions throughout immune responses.
