B-cell activation with CD40L or CpG measures the function of B-cell subsets and identifies specific defects in immunodeficient patients

Eur J Immunol. 2017 Jan;47(1):131-143. doi: 10.1002/eji.201646574. Epub 2016 Nov 25.

Abstract

Around 65% of primary immunodeficiencies are antibody deficiencies. Functional tests are useful tools to study B-cell functions in vitro. However, no accepted guidelines for performing and evaluating functional tests have been issued yet. Here, we report our experience on the study of B-cell functions in infancy and throughout childhood. We show that T-independent stimulation with CpG measures proliferation and differentiation potential of memory B cells. Switched memory B cells respond better than IgM memory B cells. On the other hand, CD40L, a T-dependent stimulus, does not induce plasma cell differentiation, but causes proliferation of naïve and memory B cells. During childhood, the production of plasmablasts in response to CpG increases with age mirroring the development of memory B cells. The response to CD40L does not change with age. In patients with selective IgA deficiency (SIgAD), we observed that switched memory B cells are reduced due to the absence of IgA memory B cells. In agreement, IgA plasma cells are not generated in response to CpG. Unexpectedly, B cells from SIgAD patients show a reduced proliferative response to CD40L. Our results demonstrate that functional tests are an important tool to assess the functions of the humoral immune system.

Keywords: B cells; Functional tests; Immunodeficiency; Pediatric immunology; Selective IgA deficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism*
  • Biomarkers
  • CD40 Antigens / metabolism
  • CD40 Ligand / immunology*
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin A / immunology
  • Immunoglobulin Class Switching
  • Immunoglobulin M / blood
  • Immunoglobulin M / immunology
  • Immunologic Deficiency Syndromes / blood
  • Immunologic Deficiency Syndromes / immunology*
  • Immunologic Deficiency Syndromes / metabolism*
  • Immunologic Memory
  • Immunophenotyping
  • Infant
  • Lymphocyte Activation / immunology*
  • Oligodeoxyribonucleotides / immunology*
  • Phenotype
  • Protein Binding
  • Receptors, Antigen, B-Cell / metabolism
  • Young Adult

Substances

  • Biomarkers
  • CD40 Antigens
  • CpG ODN 2006
  • Immunoglobulin A
  • Immunoglobulin M
  • Oligodeoxyribonucleotides
  • Receptors, Antigen, B-Cell
  • CD40 Ligand