Germ line variable regions that match hypermutated sequences in genes encoding murine anti-hapten antibodies

Genetics. 1992 Nov;132(3):799-811. doi: 10.1093/genetics/132.3.799.

Abstract

We asked whether there are germ line immunoglobulin variable (V) segments that match sites of hypermutation in V regions encoding murine antibodies. Murine germ line DNA was probed with a panel of short deoxyoligonucleotides identical in sequence to segments of hypermutated V regions from hybridomas generated in the BALB/c response to the hapten 2-phenyloxazolone (Ox). Germ line sequences that match mutations in both heavy and kappa light chain V regions were identified, and clones of some of these germ line V segments were obtained. Comparison of these clones with hypermutated V regions revealed regions of identity ranging in size from 7 to over 50 nucleotides. In an effort to separate the effects of antigen selection from the mutagenic process, we also searched for matches to a panel of silent mutations in VH regions from germinal center B cells. Fourteen silent mutations occur among a collection of 36 hypermutated VH regions from two separate germinal centers of C57BL/6 mice stimulated with the hapten 4-hydroxy-3-nitrophenyl. Matches to nine of these silent mutations can be found among published sequences of C57BL/6 VH regions of the J558 family. Taken together, these data are consistent with the possibility that a template-dependent mutational process, like gene conversion, may contribute to somatic hypermutation.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • DNA Probes
  • Gene Conversion
  • Gene Rearrangement, B-Lymphocyte
  • Genes, Immunoglobulin*
  • Genetic Variation
  • Immunoglobulin Variable Region / genetics*
  • Mice / genetics*
  • Mice / immunology
  • Mice, Inbred BALB C / genetics
  • Mice, Inbred BALB C / immunology
  • Mice, Inbred C57BL / genetics
  • Mice, Inbred C57BL / immunology
  • Molecular Sequence Data
  • Mutation
  • Oxazolone / analogs & derivatives
  • Oxazolone / immunology
  • Sequence Alignment

Substances

  • DNA Probes
  • Immunoglobulin Variable Region
  • 2-phenyloxazolone
  • Oxazolone