Rheumatoid factor.

Many human RF-associated crossreactive idiotypes (CRIs) have been defined. Since these CRIs probably are the phenotypic markers of Ig variable region genes, the data suggest that human RFs employ several Ig variable region genes which are common among outbred human populations. There are at least four types of stimuli which can trigger RF production. They are aggregated IgG in the form of antigen-antibody complexes, exogenous antigens bearing cross-reactive determinants to human IgG, autologous antibodies which mimic the Fc region of human IgG, and polyclonal B cell activators. Transient RF secretion is regularly induced by antigen-antibody complexes during secondary immune responses. In normal human subjects, RFs may be produced primarily by the B cells which bind mouse red cells, or express Leu l markers on their surface. Leu l is the human homolog of Ly l in mice. Upon polyclonal stimulation, these Ly l B cells secrete IgM autoantibodies. Combined protein and DNA sequencing studies reveal that human RFs utilize a small number of light chain variable region genes, together with several heavy chain variable regions genes. In contrast, by mRNA sequencing, murine RFs were found to employ many heavy and light chain variable region genes which belong to various gene families. Two human RF-related light chain variable region genes have been cloned and characterized. One germ-line Vk gene (designated Humkv325) is identical to four RF light chain sequences from unrelated individuals, and differs from the other eight RF light chains by one to seven amino acid residues. These results demonstrate that this RF-related Vk gene is both widely distributed and conserved among outbred human populations.