Rheumatoid factors (RFs) are autoantibodies associated with rheumatoid arthritis. They can be detected in normal individuals, although transiently. This dichotomy has led to questions about the origins and types of RFs. Recently it has been shown that B cells that produce RFs only do so when activated by two signals, one from engagement of the B-cell receptor and the other from recognition of a pathogen-associated molecular pattern through a Toll-like receptor (TLR). These autoantibodies thus link the innate and acquired immune responses.
Through a review of the literature, an examination of the current knowledge of RF induction is presented. The focus is on a discussion of a beneficial or detrimental role for RFs in normal individuals and in those with chronic disease.
What makes RF 'good' in some cases and 'bad' in others may reflect the type of RF produced. Low-affinity polyreactive IgM RFs are probably beneficial as they aid in the clearance of immune complexes that are more efficiently cleared, and the RF B cell can act as an antigen-presenting cell and stimulate host defense. However, large amounts of high-affinity RFs found in patients with chronic disease may be harmful by participation in a vicious cycle of autoantibody production by stimulation of self lymphocytes, and/or deposition in blood vessels thus causing vasculitis.
Whether RFs are beneficial or detrimental depends on the context in which they are expressed, the type and amount of RF produced, whether the response is perpetuated by TLR ligation and whether other cells are stimulated either directly or indirectly by RF-positive B cells.