Direct in vivo VH to JH rearrangement violating the 12/23 rule

J Exp Med. 2005 Feb 7;201(3):341-8. doi: 10.1084/jem.20041577.

Abstract

V(D)J recombination at the immunoglobulin heavy chain (IgH) locus follows the 12/23 rule to ensure the correct assembly of the variable region gene segments. Here, we report characterization of an in vivo model that allowed us to study recombination violating the 12/23 rule, namely a mouse strain lacking canonical D elements in its IgH locus. We demonstrate that VH to JH joining can support the generation of all B cell subsets. However, the process is inefficient in that B cells and antibodies derived from the DH-less allele are not detectable if the latter is combined with a wild-type IgH allele. There is no preferential usage of any particular VH gene family or JH element in VHJH junctions, indicating that 23/23-guided recombination is possible, but is a low frequency event at the IgH locus in vivo.

Publication types

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

MeSH terms

  • Animals
  • Antibodies / genetics
  • Antibodies / metabolism
  • B-Lymphocyte Subsets / physiology
  • B-Lymphocytes / physiology*
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain*
  • Genes, Immunoglobulin
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin Heavy Chains / metabolism
  • Immunoglobulin Variable Region / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Recombination, Genetic*

Substances

  • Antibodies
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region