Bruton's tyrosine kinase defect in dendritic cells from X-linked agammaglobulinaemia patients does not influence their differentiation, maturation and antigen-presenting cell function

Clin Exp Immunol. 2003 Jul;133(1):115-22. doi: 10.1046/j.1365-2249.2003.t01-1-02178.x.

Abstract

X-linked agammaglobulinaemia (XLA) is a primary immunodeficiency disease characterized by very low levels or even absence of circulating antibodies. The immunological defect is caused by deletions or mutations of Bruton's tyrosine kinase gene (Btk), whose product is critically involved in the maturation of pre-B lymphocytes into mature B cells. Btk is expressed not only in B lymphocytes but also in cells of the myeloid lineage, including dendritic cells (DC). These cells are professional antigen presenting cells (APC) that play a fundamental role in the induction and regulation of T-cell responses. In this study, we analysed differentiation, maturation, and antigen-presenting function of DC derived from XLA patients (XLA-DC) as compared to DC from age-matched healthy subjects (healthy-DC). We found that XLA-DC normally differentiate from monocyte precursors and mature in response to lipopolysaccharide (LPS) as assessed by de novo expression of CD83, up-regulation of MHC class II, B7.1 and B7.2 molecules as well as interleukin (IL)-12 and IL-10 production. In addition, we demonstrated that LPS stimulated XLA-DC acquire the ability to prime naïve T cells and to polarize them toward a Th1 phenotype, as observed in DC from healthy donors stimulated in the same conditions. In conclusion, these data indicate that Btk defect is not involved in DC differentiation and maturation, and that XLA-DC can act as fully competent antigen presenting cells in T cell-mediated immune responses.

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Agammaglobulinemia / genetics*
  • Agammaglobulinemia / immunology*
  • Antigen Presentation
  • Antigens, CD / analysis
  • B7-1 Antigen / analysis
  • B7-2 Antigen
  • CD83 Antigen
  • Case-Control Studies
  • Cell Cycle
  • Cell Differentiation
  • Cells, Cultured
  • Chromosomes, Human, X*
  • Dendritic Cells / enzymology*
  • Dendritic Cells / immunology
  • Histocompatibility Antigens Class II / analysis
  • Humans
  • Immunoglobulins / analysis
  • Interleukin-10 / analysis
  • Interleukin-12 / analysis
  • Lipopolysaccharides / pharmacology
  • Membrane Glycoproteins / analysis
  • Protein-Tyrosine Kinases / analysis*
  • T-Lymphocytes / immunology

Substances

  • Antigens, CD
  • B7-1 Antigen
  • B7-2 Antigen
  • CD86 protein, human
  • Histocompatibility Antigens Class II
  • Immunoglobulins
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Interleukin-10
  • Interleukin-12
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human