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

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Abstract
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.