The Rheumatoid Factor Cross-Reactive Idiotype in Juvenile Rheumatoid Arthritis: Role of the CD5-Positive B Cell

The major rheumatoid factor cross-reactive idiotype (RCRI), which was defined by prototypic monoclonal IgM rheumatoid factors (RF) from Waldenstrom's macroglobulinemia patient Wa, is present on 60% of all monoclonal IgM RF paraproteins. The RCRI is expressed in high frequency by pokeweed mitogen-derived plasma cells (PWM-PCs) and in high concentration in the sera from adults with rheumatoid arthritis (RA) who express RF in their sera. Unlike adults with RA, most children with juvenile rheumatoid arthritis (JRA) are seronegative for RF as detected by classic IgG binding assays. In the experiments summarized herein, we demonstrated that approximately 2 3 of JRA patients who are seronegative for RF, express the RCRI in high concentration in their sera and in high frequency among their PWM-PCs. Expression of this idiotype could not be attributed to expression of hidden IgM RF, or IgA RF, and may be expressed on a parallel set of immunoglobulin molecules, related to RFs, but lacking the ability to bind to IgG. There is an increased number of circulating CD5+ B cells in patients with JRA but there was no significant relationship between CD5+ B cell numbers and serum RCRI concentration, suggesting that in this disease, RCRI bearing immunoglobulins may also be produced by non-CD5+ B cells or by a small subset of CD5+ B cells.