Human monoclonal rheumatoid factors derived from the polyclonal repertoire of rheumatoid synovial tissue: incidence of cross-reactive idiotopes and expression of VH and V kappa subgroups.
A panel of 14 human monoclonal and monoreactive IgM rheumatoid factors (RF) derived from the synovial tissue of rheumatoid arthritis (RA) patients was studied for the expression of cross-reactive idiotopes (CRI) and variable heavy (VH) and variable kappa (V kappa) subgroups. Four of the twelve kappa RF expressed light chains of the V kappa III subgroup. Three of these were characterized as belonging to the V kappa IIIb sub-subgroup, and expressed the V kappa IIIb associated CRI, 17.109. None of the RF expressed the V kappa IIIa-associated CRI, 6B6.6. One of the fourteen RF expressed the VH-associated CRI, G6, and five expressed either or both the VHIII-associated CRI, B6 and D12. Seven RF bound to protein A (SpA), which indicates the expression of VHIII subgroup V regions. Together the data indicated that 9/11 RF express VHIII regions and 2/11 express VHI regions. There was no obvious correlation between V region usage or CRI expression and fine specificity of the RF for human IgG subclasses. These data indicate a difference in V gene usage by RF derived from RA patients compared with RF paraproteins derived from non-RA patients. There is not a bias towards variable chains of the V kappa III subgroup, but a marked preference for variable heavy chains of the VHIII subgroup is seen. Further studies may elucidate the pathological significance of these findings in RA.
Thompson
K M
KM
MRC Centre, Molecular Immunopathology Unit, Babraham, Cambridge.
Randen
I
I
Natvig
J B
JB
Mageed
R A
RA
Jefferis
R
R
Carson
D A
DA
Tighe
H
H
Forre
O
O
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D003429:Cross Reactions; D000939:Epitopes / Q000032:analysis; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000032:analysis*; D007130:Immunoglobulin Idiotypes / Q000032:analysis*; D007075:Immunoglobulin M / Q000032:analysis*; D007135:Immunoglobulin Variable Region / Q000032:analysis*; D051379:Mice; D012217:Rheumatoid Factor / Q000276:immunology*; D013583:Synovial Membrane / Q000276:immunology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D012217:Rheumatoid Factor