I. Ezaki et al., ANALYSIS OF THE GENES ENCODING THE VARIABLE REGIONS OF HUMAN-IGG RHEUMATOID-FACTOR, Journal of rheumatology, 21(11), 1994, pp. 2005-2010
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.