Cognate interaction with iNKT cells expands IL-10-producing B regulatory cells

Emilie E. Vomhof-DeKrey, Jennifer Yates, Thomas Hägglöf, Paula Lanthier, Eyal Amiel, Natacha Veerapen, Gurdyal S. Besra, Mikael C.I. Karlsson, Elizabeth A. Leadbetter, Michael B. Brenner

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Successful induction of B-cell activation and memory depends on help from CD4+ T cells. Invariant natural killer T (iNKT) cells (glycolipid-specific, CD1d-restricted innate lymphocytes) provide both cognate (direct) and noncognate (indirect) helper signals to enhance B-cell responses. Both forms of iNKT-cell help induce primary humoral immune responses, but only noncognate iNKT-cell help drives humoral memory and plasma cells. Here, we show that iNKT cognate help for B cells is fundamentally different from the help provided by conventional CD4+ T cells. Cognate iNKT-cell help drives an early, unsustained germinal center B-cell expansion, less reduction of T follicular regulatory cells, an expansion of marginal zone B cells, and early increases in regulatory IL-10-producing B-cell numbers compared with noncognate activation. These results are consistent with a mechanism whereby iNKT cells preferentially provide an innate form of help that does not generate humoral memory and has important implications for the application of glycolipid molecules as vaccine adjuvants.

Original languageEnglish (US)
Pages (from-to)12474-12479
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number40
DOIs
StatePublished - Oct 6 2015
Externally publishedYes

Keywords

  • B regulatory cells
  • IL-10
  • INKT cells
  • INKT follicular helper cells
  • Marginal zone B cells

ASJC Scopus subject areas

  • General

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  • Cite this

    Vomhof-DeKrey, E. E., Yates, J., Hägglöf, T., Lanthier, P., Amiel, E., Veerapen, N., Besra, G. S., Karlsson, M. C. I., Leadbetter, E. A., & Brenner, M. B. (2015). Cognate interaction with iNKT cells expands IL-10-producing B regulatory cells. Proceedings of the National Academy of Sciences of the United States of America, 112(40), 12474-12479. https://doi.org/10.1073/pnas.1504790112