Variable region gene usage of human monoclonal rheumatoid factors derived from healthy donors following immunization

Abstract

A study was performed to compare the use of immunoglobulin V gene segments by rheumatoid factors (RF) produced in physiological responses following a defined antigenic stimulus, with RF produced in rheumatoid arthritis (RA) and RF produced as monoclonal (M)-components in certain lympho-proliferative diseases. A panel of 46 monoclonal RF was produced, using hybridoma techniques, from healthy individuals following immunization 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 heavy (VH) and variable light (VL) chain gene families used by these RF were determined using idiotypic markers and polymerase chain reaction amplification with VH-specific primers. The frequencies of expression of the various gene families was compared between the two groups, and compared with the published expression frequencies seen amongst M-component RF. The majority (87%) of RF from healthy donors were found with light chains using V gene segments of the V chi 3 family, in conjunction with VH gene segments belonging to the VH1, VH3 and VH4 families. The over-expression of V chi 3, together with the distribution of VH 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 VH3 gene segments (82%) and an unbiased expression of V chi 3 segments (29% of the chi light chains). These data suggest that RF found as M-components are representative of RF used in normal physiological responses, but have undergone neoplastic or other transformation. RF found in the synovial tissue of RA patients appear to be driven by different mechanisms than RF seen in physiological responses in healthy individuals.