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.
MRC Centre, Molecular Immunopathology Unit, Babraham, Cambridge.
K M
KM
Thompson
I
I
Randen
J B
JB
Natvig
R A
RA
Mageed
R
R
Jefferis
D A
DA
Carson
H
H
Tighe
O
O
Forre
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