The influence of CD40-CD154 interactions on the expressed human V(H) repertoire: Analysis of V(H) genes expressed by individual B cells of a patient with X-linked hyper-IgM syndrome

Hans Peter Brezinschek, Thomas Dörner, Nancy L. Monson, Ruth I. Brezinschek, Peter E. Lipsky

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Analysis of the V(H)DJ(H) repertoire of peripheral blood IgM+ B cells from a patient with X-linked hyper-IgM syndrome (X-HIgM) was undertaken to determine whether the distribution of V(H) families in the productive repertoire might be regulated by in vivo CD40-CD154 interactions. The distribution of V(H) genes in the non-productive repertoire of IgM+ B cells was comparable in X-HIgM and normals. Unlike the normal productive V(H) repertoire, however, in the X-HIgM patient the V(H)4 family was found at almost the same frequency as the V(H)3 family. This reflected a diminution in the positive selection of the V(H)3 family observed in normals and the imposition of positive selection of the V(H)4 family in the X-HIgM patient. Unique among the V(H)3 genes, V(H)3-23/DP-47 was positively selected in both normals and the X-HIgM patient. No major differences in the usage of J(H) or D segments or the complementarity-determining region (CDR) 3 were noted, although the foreshortening of the CDR3 noted in the mutated V(H) rearrangements of normals was absent in the X-HIgM patient. Finally, a minor degree of somatic hypermutation was noted in the X-HIgM patient. These results have suggested that specific influences on the composition of the V(H) repertoire in normals require CD40-CD154 interactions.

Original languageEnglish (US)
Pages (from-to)767-775
Number of pages9
JournalInternational Immunology
Volume12
Issue number6
DOIs
StatePublished - Jan 1 2000

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Keywords

  • B lymphocytes
  • Ig
  • Selection
  • Somatic hypermutation
  • VDJ rearrangement

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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