Selective activation of VH3A10+ rheumatoid factor producing B cells by staphylococcal enterotoxin D.
Staphylococcal enterotoxin D (SED) is a T cell superantigen which selectively targets alpha beta TCRs bearing particular V beta 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.
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Division of Rheumatology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Brühl
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He
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Weyand
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CM
Goronzy
J J
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D000328:Adult; D000595:Amino Acid Sequence; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D002478:Cells, Cultured; D004768:Enterotoxins / Q000276:immunology*; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008969:Molecular Sequence Data; D012217:Rheumatoid Factor / Q000096:biosynthesis* / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D018089:Superantigens / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D004768:Enterotoxins; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D018089:Superantigens; C019368:enterotoxin D, Staphylococcal; D012217:Rheumatoid Factor