Impaired immunoglobulin gene rearrangement in mice lacking the IL-7 receptor

Nature. 1998 Feb 26;391(6670):904-7. doi: 10.1038/36122.


To generate the full diversity of antibody heavy-chain genes, hundreds of dispersed germline V segments must undergo recombination following D-J segment joining. Here we report that this process is regulated by the alpha-chain of the receptor for interleukin-7, a cytokine that stimulates B-cell lymphopoiesis. D-J joining occurs normally in immature B lymphocytes from mice lacking the alpha-chain of the interleukin-7 receptor (IL-7Ralpha). But recombination of V segments is progressively impaired as their distance increases upstream of D/J, causing infrequent rearrangement of most V segments, which markedly reduces diversity. This is not simply due to defective cell proliferation or impaired recombinase expression. Rather, germline transcripts from distal, unrearranged V segments, a marker of chromatin changes that precede recombination, are specifically silenced. So too is expression of Pax-5, which binds to heavy-chain locus control elements and normally stimulates recombination, suggesting a mechanism for these effects. Thus ligands of the interleukin-7 receptor deliver an extrinsic signal that targets V segment recombination in the heavy-chain locus by altering the accessibility of DNA substrates to the recombinase. This mechanism augments the recombinational diversity of the primary antibody repertoire.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Antigens, CD / physiology*
  • B-Lymphocytes / cytology
  • Bone Marrow Cells / metabolism
  • DNA Nucleotidyltransferases / metabolism
  • DNA-Binding Proteins / biosynthesis
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain / physiology*
  • Interleukin-7 / chemistry
  • Interleukin-7 / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Proteins / biosynthesis
  • PAX5 Transcription Factor
  • Polymerase Chain Reaction
  • Receptors, Interleukin / deficiency
  • Receptors, Interleukin / metabolism
  • Receptors, Interleukin / physiology*
  • Receptors, Interleukin-7
  • Recombination, Genetic
  • Transcription Factors*
  • VDJ Recombinases


  • Antigens, CD
  • DNA-Binding Proteins
  • Interleukin-7
  • Nuclear Proteins
  • PAX5 Transcription Factor
  • Pax5 protein, mouse
  • Receptors, Interleukin
  • Receptors, Interleukin-7
  • Transcription Factors
  • DNA Nucleotidyltransferases
  • VDJ Recombinases