Complement‐Fixing Intracellular Complexes of IgG Rheumatoid Factor in Rheumatoid Plasma Cells.

Abstract

Intracellular rheumatoid factor activity is found mostly in IgM plasma cells of rheumatoid synovial membranes from seropositive patients, while tissues from seronegative patients nearly always lack free rheumatoid factor. However, rheumatoid factor activity can be revealed in a considerable number of IgG plasma cells by pepsin digestion of tissues both from seropositive and seronegative patients. This activity has been further characterized by sequential double immunofluorescence staining. It was demonstrated in plasma cells representing each of the four IgG subclasses. The proportion of rheumatoid plasma cells with this activity varied in tissues from different individuals, but in some seronegative cases about 50% or more of the IgG plasma cells contained such‘hidden’ rheumatoid factor. Most of the IgG rheumatoid factors in plasma cells possessed the ability to react with several IgG subclass proteins, and were thus often directed against antigens common to two or more subclasses. The results gave evidence of intracellular blocking of rheumatoid factor activity, due to IgG‐IgG rheumatoid factor complexes. Additional evidence of such plasma cell complexes was obtained by observing an in vitro fixation of the complement components Clq and C3 to such cells. The fixation of aggregated IgG to extracellular deposits and to inclusions in synovial lining cells and joint fluid leukocytes was due to Clq as well as to rheumatoid factor.

IgG and IgM rheumatoid factor synthesis in rheumatoid synovial membrane cell cultures

“…In the 8 cultures in which IgG-RF was detectable, it represented a mean of 2.6% of the total synthesized IgG. Thus, our data are not in agreement with the results of immunofluorescence studies of synovium (1,6,24), in which IgG-RF was detected by staining in 20-60% of IgG-producing plasma cells. It is unlikely that our assay underestimated the amount of IgG-RF, since the method was standardized against a preparation of polyclonal IgG-RF that had been rigorously purified from the serum of a patient with RA (12).…”

“…IgG-RF-producing cells were demonstrated in all of 3 seronegative RA samples in 1 study (1 l), but in neither of 2 seronegative samples in the other (10). Munthe and Natvig (1,6) found that there was binding of fluoresceinated aggregated IgG to 50-75% of plasma cells of seronegative and to 25-50% of plasma cells of seropositive RA synovium after pepsin digestion. They concluded that there is extensive synthesis of self-associating IgG-RF in seropositive and seronegative rheumatoid synovial tissue.…”

“…The detection of IgM and IgG rheumatoid factors (RFs) in the synovial membrane and synovial fluid of patients with rheumatoid arthritis (RA) has suggested that local synthesis of these autoantibodies may be involved in the development of rheumatoid synovitis (1)(2)(3)(4)(5)(6). While synovial production of immunoglobulin has been demonstrated (7,8), measurement of R F synthesis has been limited because of a lack of sufficiently sensitive and specific assays.…”

The B cell repertoire of patients with rheumatoid arthritis. II. Increased frequencies of IgG+ and IgA+ B cells specific for mycobacterial heat‐shock protein 60 or human type II collagen in synovial fluid and tissue

“…Interestingly, B cells in all stages of differentiation, from mature B cells to plasma cells, have been observed (16)(17)(18)(19)(20). There is some molecular evidence that B cells are specifically activated and clonally expanded in the synovium (21)(22)(23).…”

Suppression of rheumatoid factor synthesis by antiidiotypic antibody in rheumatoid arthritis patients with cross‐reactive idiotypes

“…Idiotype-positive peripheral blood B cells may be precursors of the plasma cells that are localized in joint tissue and are producing RF (22,23). Furthermore, the positive migration inhibition with aggregated IgG in rheumatoid arthritis (24) may indicate R F idiotype-positive T cells.…”