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International Immunology, Vol. 7, No. 3, pp. 425-434,March 1995
© 1995 Japanese Society for Immunology

Selective activation of VH3A10+ rheumatoid factor producing B cells by staphylococcal enterotoxin D

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

Division of Rheumatology, Mayo Clinic and Foundation 401 Guggenheim Building, 200 First Street, SW, Rochester, MN 55905, USA

Correspondence to: Correspondence to: J. J. Goronzy

Staphylococcal enterotoxin D (SED) is a T cell superantigen which selectively targets {alpha}ß TCRs bearing particular Vß 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.

Keywords: rheumatoid factor, superantigen, T-B cell interaction, VH gene segment

Received 2 September 1994, accepted 18 November 1994.


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