The repertoire of rheumatoid factor–producing b cells in normal subjects and patients with rheumatoid arthritis

Objective. To compare the B cell repertoire of normal individuals and patients with rheumatoid arthritis (RA) and, specifically, to identify precursor B cells with the potential to secrete rheumatoid factor (RF) and to understand the T helper cell requirements for the production of this autoantibody. Methods. Frequencies of precursors of IgM, IgG, and RF‐producing B cells were measured in a limiting‐dilution system. Two distinct sources of T cell help were compared. T cell help was provided by anti‐CD3–activated CD4+ human T cell clones, or T cell–B cell interaction was facilitated by the bacterial superantigen staphylococcal enterotoxin D (SED). Results. A subset of 2–14% of peripheral blood B cells secreted IgM and IgG in SED‐driven cultures. The SED‐responsive B cell subpopulation was present at 10 times higher frequency in normal donors compared with RA patients. However, the repertoires were very similar, particularly for RF+ precursors, which represented approximately one‐third of all SED‐responsive B cells. In normal individuals, most of these RF+ precursor B cells did not respond to anti‐CD3–activated T helper cells, with only a very small fraction of B cells activated by anti‐CD3–driven helper cells maturing into RF‐secreting B cells (from 1 of 182 to 1 of 889 IgM‐producing B cells). This subset was expanded approximately 50‐fold in RA patients. Conclusion. Normal subjects and RA patients share a pool of B cells which secrete RF when activated in the presence of SED and T helper cells. These B cells are frequent and obviously anergic in normal individuals. The B cell subset with the potential to produce RF when help is provided in noncognate T–B interaction (anti‐CD3–driven T cells) is considerably expanded in RA patients, probably reflecting an increased responsiveness of such B cells to helper signals.