Reduction of CD1d expression in vivo minimally affects NKT-enhanced antibody production but boosts B-cell memory

Int Immunol. 2011 Apr;23(4):251-60. doi: 10.1093/intimm/dxq477. Epub 2011 Mar 12.

Abstract

The CD1d-binding glycolipid α-galactosylceramide exerts potent adjuvant effects on T-dependent humoral immunity. The mechanism is driven by cognate interaction between CD1d-expressing B cells and TCR-expressing type I CD1d-restricted NKT cells. Thus, far positive effects of alpha-galactosylceramide have been observed on initial and sustained antibody titers as well as B-cell memory. Following vaccination, each of these features is desirable, but good B-cell memory is of paramount importance for long-lived immunity. We therefore tested the hypothesis that CD1d expression in vivo differentially affects initial antibody titers versus B-cell memory responses. CD1d(+/+) and CD1d(+/-) mice were generated and immunized with antigen plus CD1d ligand before analysis of cytokine expression, CD40L expression, initial and longer term antibody responses and B-cell memory. As compared with CD1d(+/+) controls, CD1d(+/-) mice had equivalent numbers of total NKT cells, lower cytokine production, fewer CD40L-expressing NKT cells, lower initial antibody responses, similar long-term antibody responses and higher B-cell memory. Our data indicate that weak CD1d antigen presentation may facilitate good B-cell memory without compromising antibody responses. This work may impact vaccine design since over-stimulation of NKT cells at the time of vaccination may not lead to optimal B-cell memory.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation / genetics
  • Antigens, CD1d / genetics
  • Antigens, CD1d / immunology
  • Antigens, CD1d / metabolism*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • CD40 Ligand / genetics
  • CD40 Ligand / metabolism
  • Cell Communication
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / metabolism
  • Female
  • Galactosylceramides / immunology
  • Galactosylceramides / metabolism
  • Immunologic Memory / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Natural Killer T-Cells / cytology
  • Natural Killer T-Cells / immunology
  • Natural Killer T-Cells / metabolism*

Substances

  • Antigens, CD1d
  • Cytokines
  • Galactosylceramides
  • alpha-galactosylceramide
  • CD40 Ligand