Decreased TNF family receptor expression on B-cells is associated with reduced humoral responses to Streptococcus pneumoniae infections in young children

Cell Immunol. 2017 Oct:320:11-19. doi: 10.1016/j.cellimm.2017.07.004. Epub 2017 Jul 21.

Abstract

An underdeveloped or impaired immune response in young children is associated with increased susceptibility to Streptococcus pneumonia (Spn) infections. We determined serum antibody titers against 3 Spn vaccine candidate proteins and vaccine serotype polysaccharide antigens in a group of Spn infection prone 9-18months old and found lower IgG antibody titers to all tested antigens compared to age-matched non-infection-prone children. We also found the children had significantly reduced percentages of total memory B-cells, switched memory B-cells and plasma cells. We sought a mechanistic explanation for that result by examination of TNF family receptors (TNFRs) TACI, BCMA, and BAFFR receptor expression on B-cells and found significantly lower BAFFR and TACI expression; significantly lower proliferation of B-cells stimulated with exogenous BAFF; and diminished expression of co-stimulatory receptors B7-1 and B7-2 among infection prone vs. non-prone children. We conclude that lower expression of TNFRs, lower proliferation of B-cells in response to BAFF and lower expression of B7-1 and B7-2 by B-cells may contribute to reduced antibody responses to Spn and consequent infection proneness in young children.

Keywords: Acute otitis media; B-cell activating factor receptor; B-cell maturation antigen; Calcium-modulator; Cytophilin ligand interactor; Transmembrane activator.

MeSH terms

  • Antibodies, Bacterial / blood
  • B-Cell Activation Factor Receptor / metabolism*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / microbiology
  • B7-1 Antigen / metabolism
  • B7-2 Antigen / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Disease Susceptibility
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Immunologic Memory
  • Infant
  • Lymphocyte Activation
  • Male
  • Otitis / immunology*
  • Pneumococcal Infections / immunology*
  • Pneumococcal Vaccines / immunology*
  • Streptococcus pneumoniae / immunology*
  • Transmembrane Activator and CAML Interactor Protein / metabolism*
  • Vaccination

Substances

  • Antibodies, Bacterial
  • B-Cell Activation Factor Receptor
  • B7-1 Antigen
  • B7-2 Antigen
  • Immunoglobulin G
  • Pneumococcal Vaccines
  • TNFRSF13B protein, human
  • TNFRSF13C protein, human
  • Transmembrane Activator and CAML Interactor Protein