title: Follicular helper NKT cells induce limited B cell responses and germinal center formation in the absence of CD4(+) T cell help.
abstract: 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 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 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.
authors.affiliation: Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Tonti
authors.forename: Maya
authors.initials: M
authors.lastname: Fedeli
authors.forename: Anna
authors.initials: A
authors.lastname: Napolitano
authors.forename: Matteo
authors.initials: M
authors.lastname: Iannacone
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: von Andrian
authors.forename: Luca G
authors.initials: LG
authors.lastname: Guidotti
authors.forename: Sergio
authors.initials: S
authors.lastname: Abrignani
authors.forename: Giulia
authors.initials: G
authors.lastname: Casorati
authors.forename: Paolo
authors.initials: P
authors.lastname: Dellabona
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000917:Antibody Formation; D055610:Antigens, CD1d / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D005699:Galactosylceramides / Q000494:pharmacology; D005802:Genes, MHC Class II; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008211:Lymphocyte Cooperation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D006377:T-Lymphocytes, Helper-Inducer
chemical_list: D055610:Antigens, CD1d; C526879:Cd1d1 protein, mouse; D005699:Galactosylceramides; D007074:Immunoglobulin G; C493154:alpha-galactosylceramide