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 super-antigen 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.