Antigen receptor engagement turns off the V(D)J recombination machinery in human tonsil B cells

J Exp Med. 1998 Aug 17;188(4):765-72. doi: 10.1084/jem.188.4.765.

Abstract

The germinal center (GC) is an anatomic compartment found in peripheral lymphoid organs, wherein B cells undergo clonal expansion, somatic mutation, switch recombination, and reactivate immunoglobulin gene V(D)J recombination. As a result of somatic mutation, some GC B cells develop higher affinity antibodies, whereas others suffer mutations that decrease affinity, and still others may become self-reactive. It has been proposed that secondary V(D)J rearrangements in GCs might rescue B cells whose receptors are damaged by somatic mutations. Here we present evidence that mature human tonsil B cells coexpress conventional light chains and recombination associated genes, and that they extinguish recombination activating gene and terminal deoxynucleotidyl transferase expression when their receptors are cross-linked. Thus, the response of the recombinase to receptor engagement in peripheral B cells is the opposite of the response in developing B cells to the same stimulus. These observations suggest that receptor revision is a mechanism for receptor diversification that is turned off when antigen receptors are cross-linked by the cognate antigen.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / metabolism*
  • CD40 Antigens / metabolism
  • Cells, Cultured
  • DNA Nucleotidylexotransferase / biosynthesis
  • DNA-Binding Proteins / biosynthesis
  • Homeodomain Proteins / biosynthesis
  • Humans
  • Immunoglobulin Joining Region / genetics*
  • Immunoglobulin Light Chains
  • Immunoglobulin Light Chains, Surrogate
  • Immunoglobulin Variable Region / genetics*
  • Immunoglobulin kappa-Chains / immunology
  • Immunoglobulin lambda-Chains / immunology
  • Membrane Glycoproteins / biosynthesis
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Proteins
  • Palatine Tonsil / cytology
  • Receptors, Antigen, B-Cell / metabolism*
  • Recombination, Genetic*

Substances

  • CD40 Antigens
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Immunoglobulin Joining Region
  • Immunoglobulin Light Chains
  • Immunoglobulin Light Chains, Surrogate
  • Immunoglobulin Variable Region
  • Immunoglobulin kappa-Chains
  • Immunoglobulin lambda-Chains
  • Membrane Glycoproteins
  • Nuclear Proteins
  • RAG2 protein, human
  • Rag2 protein, mouse
  • Receptors, Antigen, B-Cell
  • V(D)J recombination activating protein 2
  • RAG-1 protein
  • DNA Nucleotidylexotransferase