RP105‐lacking B cells from lupus patients are responsible for the production of immunoglobulins and autoantibodies

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Abstract
Objective We previously reported that B cells lacking the RP105 molecule, which proved to be highly activated B cells, are increased in the peripheral blood of patients with systemic lupus erythematosus (SLE). In the present study, we attempted to determine whether RP105‐negative B cells obtained from SLE patients would be capable of producing autoantibodies as well as immunoglobulins. Methods RP105‐positive and RP105‐negative B cells, sorted by cell sorter, were cultured for 5 days without stimulation, or were stimulated with Staphylococcus aureus Cowan 1 strain (SAC) or recombinant interleukin‐6 (IL‐6). For the assay of autoantibodies, RP105‐positive and RP105‐negative B cells were cultured separately for 10 days with anti‐CD3 antibody–stimulated T cells. The production of immunoglobulins and autoantibodies was determined by enzyme‐linked immunosorbent assay. Results We demonstrated that RP105‐negative B cells, but not RP105‐positive B cells, obtained from SLE patients could spontaneously produce IgG and IgM in vitro until day 5. SAC and IL‐6 enhanced production of IgG and IgM by RP105‐negative B cells but failed to induce such production by RP105‐positive B cells. The latter cells, however, when cocultured with activated T cells in the presence of IL‐10, produced IgG, although the amount was very small compared with that produced by RP105‐negative B cells. Most important, under these conditions, anti–double‐stranded DNA antibodies were produced only by the RP105‐negative B cells obtained from SLE patients. Conclusion These data indicate that RP105‐negative B cells, constituting a subset of B cells in SLE patients, are highly activated and may be responsible for the production of autoantibodies as well as polyclonal immunoglobulins.