A. Wong et al., HUMAN MONOCLONAL RHEUMATOID-FACTOR DERIVED FROM RHEUMATOID SYNOVIAL-CELLS MONOSPECIFIC FOR RABBIT IGG, Journal of rheumatology, 20(4), 1993, pp. 623-629
Rheumatoid factors (RF) in rheumatoid arthritis (RA) are polyclonal au
toantibodies directed against antigenic epitopes located in the Fc por
tion of the IgG molecule. Hybridoma technology has overcome the diffic
ulty of their polyclonality, so that monoclonal RF (mRF) can be examin
ed for their individual binding specificities and genetics. We isolate
d a monoclonal IgM RF secreting hybridoma (designated H4) from the rhe
umatoid synovial cells (RSC) of a patient with RA. H4 bound specifical
ly with rabbit IgG (RIgG) and had no human IgG (HIgG) reactivity. By d
irect binding ELISA and absorption experiments, 6% of the RIgG reactiv
e RSC RF in this patient with RA was monospecific for RIgG. H4 was tes
ted against RIgG F(ab')2 and pFc' fragments, and bound only to the pFc
' fragment (CH3 domain). Moreover, H4 mRF had high avidity for RIgG in
a capture ELISA. Total RNA was extracted and the variable region heav
y (VH) and light (VL) chain cDNA were amplified using polymerase chain
reaction technology. Sequence analysis of the IgM RF VH and VL chain
genes indicated usage of the VH26 germline gene (VhIII gene family) an
d a new Vlambda germline gene. Our results suggest preferential use of
restricted germline genes in the formation of autoantibodies in human
autoimmune diseases. The pathological significance of RIgG specific R
F is still unclear. However, this finding suggests that all RSC RF pro
duction may not necessarily be induced by autologous IgG.