Sequence homologies, N sequence insertion and JH gene utilization in VHDJH joining: implications for the joining mechanism and the ontogenetic timing of Ly1 B cell and B-CLL progenitor generation

EMBO J. 1990 Jul;9(7):2133-40.

Abstract

Sequence analysis of rearranged VHDJH genes of B lineage cells from various stages of ontogeny indicates that short sequence homologies at the breakpoints of recombination contribute to V region gene assembly. Such homologies are regularly seen at DJH junctions of neonatal pre-B cells, most of which do not contain N sequences. In the same cells, but not at later developmental stages, preferential usage of the JH1 element is observed. After birth, N sequence insertion increases with time and is always more prominent at the VHD border than the DJH border. In pre-B cells from adult animals and in mature B cells, in cases where N sequences were not detectable, sequence homologies at the DJH border were found in only half of the instances. This lower incidence could be due to N sequence addition to one of the recombining DNA ends and/or cellular selection. Inspection of VHDJH junctions for N sequence insertion, sequence homologies at the DJH border and JH1 usage allows the estimation of the timepoint in ontogeny at which particular B cell subsets are seeded into the immune system. Specifically, the present data show that the cells of the Ly1 B cell subset are generated not only neonatally but also beyond the first weeks of life. However, the DJH junctions of the progenitors of chronic B cell leukemias which originate from the same B cell subset resemble those of neonatal pre-B cells, suggesting that these cells have already undergone a transforming event at this early developmental stage.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Antigens, Ly / immunology*
  • B-Lymphocytes / immunology*
  • Base Sequence
  • Gene Amplification
  • Gene Library
  • Gene Rearrangement*
  • Genes, Immunoglobulin
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin Variable Region / genetics*
  • Mice
  • Mice, Inbred Strains
  • Molecular Sequence Data
  • Oligonucleotide Probes
  • Polymerase Chain Reaction
  • Sequence Homology, Nucleic Acid

Substances

  • Antigens, Ly
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • Oligonucleotide Probes