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

J Immunol. 2012 Apr 1;188(7):3217-22. doi: 10.4049/jimmunol.1103501. Epub 2012 Feb 29.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibody Formation
  • Antigens, CD1d / immunology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / transplantation
  • Galactosylceramides / pharmacology
  • Genes, MHC Class II
  • Germinal Center / cytology
  • Germinal Center / immunology*
  • Immunization
  • Immunoglobulin G / biosynthesis
  • Lymphocyte Activation / drug effects
  • Lymphocyte Cooperation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Natural Killer T-Cells / immunology*
  • Specific Pathogen-Free Organisms
  • T-Lymphocytes, Helper-Inducer

Substances

  • Antigens, CD1d
  • Cd1d1 protein, mouse
  • Galactosylceramides
  • Immunoglobulin G
  • alpha-galactosylceramide