ANALYSIS OF THE GENES ENCODING THE VARIABLE REGIONS OF HUMAN-IGG RHEUMATOID-FACTOR

Objective. To better understand the immunoglobulin variable (V) region repertoire of rheumatoid factors (RF). Methods. We characterized the heavy (H) and light (L) chain gene segments utilized in a monospecific IgG RF secreting hybridoma (AEE111F) which were derived from a patien t with rheumatoid arthritis (RA). The hybridoma was established by fus ion of a mouse myeloma cell line with bone marrow derived mononuclear cells from a patient with RA. First strand complementary DNA (cDNA) wa s generated and used for a polymerase chain reaction amplification of the H and L chain V domains. The amplified V domains were sequenced an d compared with an extensive database of germline and cDNA V gene segm ents. Results. The VH sequence was found to be 96% homologous to a pre viously described fetal VH3 cDNA (60P2). The VL sequence was also high ly homologous to the previously described V lambda II gene (96%) deriv ed from a patient with systemic lupus erythematosus which correlated w ith an 8.12 idiotype (Id), and to an antibacterial antibody against th e Haemophilus influenzae type b capsular polysaccharide (94.7%). Concl usion. The overlap among this RF VL gene and the 2 reported V lambda s equences of antibodies that expressed anti-DNA related Id and an envir onmental pathogen specificity suggests that a part of the IgG RF isola ted from patients with RA may thus be derived from the physiological n atural antibody repertoire during an abnormal immune response and then develop high affinity, monospecific RF by the selection of an antigen driven mechanism.