VARIABLE REGION GENE USAGE OF HUMAN MONOCLONAL RHEUMATOID FACTORS DERIVED FROM HEALTHY DONORS FOLLOWING IMMUNIZATION

A study was performed to compare the use of immunoglobulin V gene segm ents by rheumatoid factors (RF) produced in physiological responses fo llowing a defined antigenic stimulus, with RF produced in rheumatoid a rthritis (RA) and RF produced as monoclonal (M)-components in certain lympho-proliferative diseases. A panel of 46 monoclonal RF was produce d, using hybridoma techniques, from healthy individuals following immu nization with foreign antigens (mis-matched red blood cells). A panel of previously characterized monoclonal RF from RA synovial tissues was extended to a total of 24 and included in the study. The variable hea vy (V-H) and variable light (V-L) chain gene families used by these RF were determined using idiotypic markers and polymerase chain reaction amplification with V-H-specific primers. The frequencies of expressio n of the various gene families was compared between the two groups, an d compared with the published expression frequencies seen amongst M-co mponent RE The majority (87 %) of RF from healthy donors were found wi th light chains using V gene segments of the V kappa 3 family, in conj unction with VH gene segments belonging to the V(H)1,V(H)3 and V(H)4 f amilies. The over-expression of V kappa 3, together with the distribut ion of V-H families, demonstrates close similarities with RF found as M-components in lympho-proliferative diseases. In contrast, RF from RA patients showed a predominant use of V(H)3 gene segments (82 %) and a n unbiased expression of V kappa 3 segments (29 % of the kappa light c hains). These data suggest that RF found as M-components are represent ative of RF used in normal physiological responses, but have undergone neoplastic or other transformation. RF found in the synovial tissue o f RA patients appear to be driven by different mechanisms than RF seen in physiological responses in healthy individuals.