Bruton's tyrosine kinase is essential for human B cell tolerance

J Exp Med. 2004 Oct 4;200(7):927-34. doi: 10.1084/jem.20040920.

Abstract

Most polyreactive and antinuclear antibodies are removed from the human antibody repertoire during B cell development. To elucidate how B cell receptor (BCR) signaling may regulate human B cell tolerance, we tested the specificity of recombinant antibodies from single peripheral B cells isolated from patients suffering from X-linked agammaglobulinemia (XLA). These patients carry mutations in the Bruton's tyrosine kinase (BTK) gene that encode an essential BCR signaling component. We find that in the absence of Btk, peripheral B cells show a distinct antibody repertoire consistent with extensive secondary V(D)J recombination. Nevertheless, XLA B cells are enriched in autoreactive clones. Our results demonstrate that Btk is essential in regulating thresholds for human B cell tolerance.

Publication types

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

MeSH terms

  • Adult
  • Agammaglobulinaemia Tyrosine Kinase
  • Agammaglobulinemia / immunology*
  • Antibodies / immunology*
  • B-Lymphocytes / immunology*
  • Cell Separation
  • Child
  • DNA, Complementary / genetics
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Fluorescent Antibody Technique, Indirect
  • Genetic Diseases, X-Linked / immunology*
  • Humans
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / immunology*

Substances

  • Antibodies
  • DNA, Complementary
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human