Anti–�-globulins or rheumatoid factors (RF) were first described in the early 1940s. They are present in �70% of patients with rheumatoid arthritis (RA) and high titers are associated with severe disease, but they also appear in a large number of other diseases including viral, bacterial, and parasitic infections (1). In spite of their wide spread occurrence, it is still a puzzle how or why RF are generated. RF come in two varieties. Low affinity RF (Kd of �10�5 M) are IgM natural antibodies with specificity for IgG-Fc determinants and cross-reactivity with other autoantigens, i.e., polyreactivity. They are produced by CD5 � B cells in normal subjects (2). Frequently they are IgM � antibodies and use selected germline V genes for both H and L chains. This is why they share cross-reactive idiotypes, as discovered by Kunkel et al. in the 1970s (3). These antibodies are typically T cell independent. They are simila
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