Reactivity and self-association in vivo of a human monoclonal IgG rheumatoid factor.
In order to study the pathogenic potential of IgG rheumatoid factor (IgG-RF) we generated a human monoclonal IgG4-RF-producing cell line, OR-1, by Epstein-Barr virus transformation of B cells derived from a healthy donor. Characterization of OR-1 RF specificity demonstrated that this RF binds only to IgG and not to dsDNA or seven different proteins tested. Although both OR-1 RF and C1q bind to the Fc part of IgG, no influence could be observed of OR-1 RF on the complement-fixing potential of heat-aggregated IgG, suggesting that OR-1 RF does not interfere with C1q binding to IgG. This was confirmed by blocking studies which showed that binding of OR-1 RF to IgG could be prevented by Staphylococcal protein A (SpA), but not by C1q. Comparison of OR-1 RF with SpA regarding their ability to bind to IgG derived from different species and human IgG subclasses demonstrated that OR-1 RF and SpA have an identical IgG specificity. The possibility that a structural homology exists between SpA and OR-1 RF was ruled out, however, by using affinity-purified chicken anti-SpA antibodies, which were not able to bind to OR-1 RF. The potential of self-recognition of OR-1 RF in vivo was examined by injecting OR-1 cells in SCID mice. Two months after injection IgG-RF was present in the circulation in monomeric, dimeric and polymeric forms whereas circulating IgG without RF activity, derived from an injected control cell line, was present in the monomeric form only. In vitro studies indicated that IgG-RF is secreted in monomeric form and that polymerization is a concentration-dependent phenomenon. The fact that IgG-RF is able to form immune complexes in vivo indicates that IgG-RF has a pathogenic potential by itself and therefore IgG-RF may play a role in the pathogenesis of RA.
Otten
H G
HG
Department of Rheumatology, University Hospital, Leiden, The Netherlands.
Daha
M R
MR
De Rooy
H H
HH
Breedveld
F C
FC
D000818:Animals; D000918:Antibody Specificity; D002460:Cell Line; D003167:Complement Activation; D000939:Epitopes; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology*; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D051379:Mice; D016513:Mice, SCID; D011485:Protein Binding; D011961:Receptors, Fc / Q000378:metabolism; D012217:Rheumatoid Factor / Q000737:chemistry / Q000276:immunology*
D000939:Epitopes; D007074:Immunoglobulin G; D046911:Macromolecular Substances; D011961:Receptors, Fc; D012217:Rheumatoid Factor