Antigen presentation by B cells guides programing of memory CD4 + T-cell responses to a TLR4-agonist containing vaccine in mice

Eur J Immunol. 2016 Dec;46(12):2719-2729. doi: 10.1002/eji.201646399. Epub 2016 Nov 9.

Abstract

The contribution of B cells to immunity against many infectious diseases is unquestionably important and well characterized. Here, we sought to determine the role of B cells in the induction of T-helper 1 (TH 1) CD4+ T cells upon vaccination with a tuberculosis (TB) antigen combined with a TLR4 agonist. We used B-cell deficient mice (μMT-/- ), tetramer-positive CD4+ T cells, markers of memory "precursor" effector cells (MPECs), and T-cell adoptive transfers and demonstrated that the early antigen-specific cytokine-producing TH 1 responses are unaffected in the absence of B cells, however MPEC induction is strongly impaired resulting in a deficiency of the memory TH 1 response in μMT-/- mice. We further show that antigen-presentation by B cells is necessary for their role in MPEC generation using B-cell adoptive transfers from wt or MHC class II knock-out mice into μMT-/- mice. Our study challenges the view that B-cell deficiency exclusively alters the TH 1 response at memory time-points. Collectively, our results provide new insights on the multifaceted roles of B cells that will have a high impact on vaccine development against several pathogens including those requiring TH 1 cell-mediated immunity.

Keywords: B cells · T cells · μMT−/− mice · memory precursor effector cells · TLR4 agonist.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigen Presentation*
  • B-Lymphocytes / physiology*
  • B-Lymphocytes / transplantation
  • Cell Differentiation
  • Cells, Cultured
  • Humans
  • Immunoglobulin mu-Chains / genetics
  • Immunologic Factors / immunology*
  • Immunologic Memory
  • Lymphocyte Activation
  • Mice
  • Mice, Knockout
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / transplantation
  • Th1 Cells / immunology*
  • Toll-Like Receptor 4 / agonists
  • Tuberculosis / immunology*
  • Tuberculosis / prevention & control
  • Tuberculosis Vaccines / immunology*

Substances

  • Immunoglobulin mu-Chains
  • Immunologic Factors
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Tuberculosis Vaccines