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Publication : Follicular helper NKT cells induce limited B cell responses and germinal center formation in the absence of CD4(+) T cell help.

First Author  Tonti E Year  2012
Journal  J Immunol Volume  188
Issue  7 Pages  3217-22
PubMed ID  22379027 Mgi Jnum  J:183101
Mgi Id  MGI:5317485 Doi  10.4049/jimmunol.1103501
Citation  Tonti E, et al. (2012) Follicular helper NKT cells induce limited B cell responses and germinal center formation in the absence of CD4(+) T cell help. J Immunol 188(7):3217-22
abstractText  B cells require MHC class II (MHC II)-restricted cognate help and CD40 engagement by CD4(+) T follicular helper (T(FH)) 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 alpha-galactosylceramide (alphaGalCer). We previously observed that immunization of mice lacking CD4(+) T cells (MHC II(-/-)) elicits specific IgG responses only when protein Ags are mixed with alphaGalCer. 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 alphaGalCer 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 CXCR5(hi)programmed death-1(hi)ICOS(hi)Bcl-6(hi) T(FH) 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 iNKT(FH) 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 iNKT(FH) and CD4(+) T(FH) cells display distinct helper features, consistent with the notion that these two cell subsets play nonredundant functions throughout immune responses.
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