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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.

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.
AuthorsH P Brezinschek, T Dörner, N L Monson, R I Brezinschek, P E Lipsky
JournalInternational immunology (Int Immunol) Vol. 12 Issue 6 Pg. 767-75 (Jun 2000) ISSN: 0953-8178 [Print] England
PMID10837404 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • CD40 Antigens
  • Immunoglobulin Heavy Chains
  • Immunoglobulin M
  • Immunoglobulin Variable Region
  • Membrane Glycoproteins
  • CD40 Ligand
Topics
  • CD40 Antigens (physiology)
  • CD40 Ligand
  • Child, Preschool
  • Genes, Immunoglobulin
  • Genetic Linkage
  • Humans
  • Hypergammaglobulinemia (genetics)
  • Immunoglobulin Heavy Chains (genetics)
  • Immunoglobulin M (blood)
  • Immunoglobulin Variable Region (genetics)
  • Male
  • Membrane Glycoproteins (physiology)
  • Mutation
  • X Chromosome

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