Cross-reactivity of IgG anti-DNA-secreting B cells in patients with systemic lupus erythematosus.

This study is the first to analyze the cross-reactivity of in vivo activated B cells from patients with systemic lupus erythematosus. A chamber ELIspot assay was used to determine whether lymphocytes secreting antibodies that bound to DNA or 2,4,6-trinitrophenol (TNP)-keyhole limpet-hemocyanin (KLH) could simultaneously bind to the unrelated antigens actin or ovalbumin. IgM anti-DNA-, IgM anti-TNP-KLH- and IgG anti-TNP-KLH-secreting B cells from patients and controls showed similar levels of cross-reactivity (ranging from 6% to 23%, depending upon the antibody isotype and antigen pair examined). In general, IgG-producing cells were less cross-reactive than IgM producers from the same individual (on the average threefold, p < 0.001). In contrast, IgG anti-DNA-secreting B cells from lupus patients (i) showed no decrease in cross-reactivity when compared to IgM anti-DNA-secreting cells and (ii) were significantly more cross-reactive than control IgG anti-DNA-secreting cells and IgG anti-TNP-KLH secreting cells from patients (p < 0.001). The degree of IgG anti-DNA cross-reactivity correlated with disease activity (r = 0.52, p < 0.02). The implications of these findings with respect to repertoire expression and disease pathogenesis are discussed.