A mouse with a monoclonal primary immunoglobulin repertoire not further diversified by V-gene replacement

Dev Immunol. 1999;7(1):43-50. doi: 10.1155/1999/24514.

Abstract

We have generated a monoclonal B-cell mouse by introducing homozygous, nonfunctional RAG-2 alleles and a lambda1 light-chain transgene into the quasi-monoclonal (QM) mouse, which contains a "knocked-in" V(H)DJ(H) rearrangement. Thus, this mouse, which we call MonoB, is devoid of T cells and contains preformed heavy- and light-chain genes encoding immunoglobulin with an anti-NP specificity. The MonoB mouse allows us to examine immunoglobulin diversity in the absence of processes mediated by V(D)J recombination and T cells. Here we report that not only is the MonoB's primary immunoglobulin repertoire monoclonal, but also that its secondary repertoire is not further diversified by V-gene replacement or gene conversion. Among 99 heavy-chain and 41 lambda light-chain genes from peripheral B cells of the MonoB mouse, there were no V-gene replacements. When compared to the QM mouse, which has RAG activity, and for which V-gene replacement is the major diversifying mechanism, these data suggest that V-gene replacement is mediated by V(D)J recombination and not by other recombination systems.

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Gene Rearrangement, B-Lymphocyte*
  • Genetic Variation
  • Immunoglobulin Isotypes / genetics*
  • Immunoglobulin Isotypes / immunology*
  • Immunoglobulin Variable Region / genetics*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic

Substances

  • Immunoglobulin Isotypes
  • Immunoglobulin Variable Region