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

Academic Article
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Overview

authors

  • Tonti, E.
  • Fedeli, M.
  • Napolitano, A.
  • Iannacone, M.
  • von Andrian, U. H.
  • Guidotti, Luca
  • Abrignani, S.
  • Casorati, G.
  • Dellabona, P.

publication date

  • April 2012

journal

  • Journal of Immunology  Journal

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.

subject areas

  • Adoptive Transfer
  • Animals
  • Antibody Formation
  • Antigens, CD1d
  • B-Lymphocytes
  • Galactosylceramides
  • Genes, MHC Class II
  • Germinal Center
  • Immunization
  • Immunoglobulin G
  • Lymphocyte Activation
  • Lymphocyte Cooperation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Natural Killer T-Cells
  • Specific Pathogen-Free Organisms
  • T-Lymphocytes, Helper-Inducer
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Identity

PubMed Central ID

  • PMC3559029

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1103501

PubMed ID

  • 22379027
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Additional Document Info

start page

  • 3217

end page

  • 3222

volume

  • 188

issue

  • 7

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