Selective activation of Vh3A10+ rheumatoid factor producing B cells by staphylococcal enterotoxin D

Congping Xie, Hilke Brühl, Xiaowen He, Cornelia M. Weyand, Jörg J. Goronzy

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Staphylococcal enterotoxin D (SED) is a T cell superantigen which selectively targets αβ TCRs bearing particular Vβ elements. A second function of SED relates to the preferential activation of a B cell subset characterized by a high frequency of rheumatoid factor (RF) producing B cells. To define the molecular basis of the SED-induced B cell repertoire shift, we have analyzed Ig heavy chain genes in B cell clones expanded after SED stimulation and compared them with B cell clones established in the presence of anti-CD3 stimulated helper cells. Gene segments of the VH3 family were most frequently utilized under both stimulation conditions (42% anti-CD3; 47% SED). Sequence analysis of VH3 gene segments demonstrated that the repertoire of VH3 elements in B cell clones from SED driven and anti-CD3 driven cultures were distinct (P=0.01). RF activity was closely associated with the expression of selected VH3 elements. B cell clones stimulated with SED preferentially expressed VH3A10, whereas VH26 was the gene segment dominantly used in B cell clones expanded with anti-CD3 stimulated helper cells. The usage of JH and DH elements was indistinguishable in SED and anti-CD3 driven B cell clones, suggesting that SED targets VH3+ B cells through a VH-specific mechanism. Comparison of the closely related sequences of the SED responsive VH3A10 and the SED non-responsive VH26 element suggested a role of a sequence polymorphism in the CDR2 reminiscent of B cell reactivity to conventional antigens. In contrast to conventional antigens, SED can induce differentiation of a high frequency of naive B cells. Thus, this staphylococcal enterotoxin combines selective activation of T cells with selective activation of B cells and might be able to direct T cell help to RF producing B cells.

Original languageEnglish (US)
Pages (from-to)425-434
Number of pages10
JournalInternational Immunology
Volume7
Issue number3
DOIs
StatePublished - Mar 1995

Keywords

  • Rheumatoid factor
  • Superantigen
  • T-B cell interaction
  • VH gene segment

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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