Importance of B cell co-stimulation in CD4(+) T cell differentiation: X-linked agammaglobulinaemia, a human model

Clin Exp Immunol. 2011 Jun;164(3):381-7. doi: 10.1111/j.1365-2249.2011.04377.x. Epub 2011 Apr 13.

Abstract

We were interested in the question of whether the congenital lack of B cells actually had any influence on the development of the T cell compartment in patients with agammaglobulinaemia. Sixteen patients with X-linked agammaglobulinaemia (XLA) due to mutations in Btk, nine patients affected by common variable immune deficiency (CVID) with <2% of peripheral B cells and 20 healthy volunteers were enrolled. The T cell phenotype was determined with FACSCalibur and CellQuest Pro software. Mann-Whitney two-tailed analysis was used for statistical analysis. The CD4 T cell memory compartment was reduced in patients with XLA of all ages. This T cell subset encompasses both CD4(+)CD45RO(+) and CD4(+)CD45RO(+)CXCR5(+) cells and both subsets were decreased significantly when compared to healthy controls: P = 0·001 and P < 0·0001, respectively. This observation was confirmed in patients with CVID who had <2% B cells, suggesting that not the lack of Bruton's tyrosine kinase but the lack of B cells is most probably the cause of the impaired CD4 T cell maturation. We postulate that this defect is a correlate of the observed paucity of germinal centres in XLA. Our results support the importance of the interplay between B and T cells in the germinal centre for the activation of CD4 T cells in humans.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Agammaglobulinaemia Tyrosine Kinase
  • Agammaglobulinemia / diagnosis
  • Agammaglobulinemia / genetics
  • Agammaglobulinemia / immunology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / pathology
  • Cell Differentiation
  • Cell Separation
  • Child
  • Common Variable Immunodeficiency / diagnosis
  • Common Variable Immunodeficiency / genetics
  • Common Variable Immunodeficiency / immunology*
  • Female
  • Flow Cytometry
  • Genetic Diseases, X-Linked / diagnosis
  • Genetic Diseases, X-Linked / genetics
  • Genetic Diseases, X-Linked / immunology
  • Humans
  • Immunologic Memory
  • Leukocyte Common Antigens / biosynthesis
  • Lymphocyte Depletion
  • Male
  • Middle Aged
  • Mutation / genetics
  • Protein-Tyrosine Kinases / genetics
  • Receptors, CXCR5 / biosynthesis

Substances

  • CXCR5 protein, human
  • Receptors, CXCR5
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • Leukocyte Common Antigens

Supplementary concepts

  • Bruton type agammaglobulinemia