Induction of arthritis by single monoclonal IgG anti-collagen type II antibodies and enhancement of arthritis in mice lacking inhibitory FcgammaRIIB.
IgG anti-collagen type II (CII) antibodies (Ab) can induce arthritis in healthy mice. Here we have investigated if single monoclonal IgG anti-CII Ab can induce arthritis in CIA-susceptible DBA/1 mice and if there is an IgG subclass dependency. The involvement of Fc receptors for IgG (FcgammaR) in anti-CII Ab-mediated arthritis was also investigated by comparing the clinical outcome in DBA/1 mice to those in FcgammaR-deficient mice. We demonstrate for the first time that single mAb to naive DBA/1 mice can induce persistent arthritis. Histology of the inflamed joints revealed massive cellular infiltrate and cartilage and bone destruction. All IgG subclasses tested (IgG1, IgG2a and IgG2b) were arthritogenic, with the IgG1 and IgG2b isotypes as the dominating arthritogenic Ab. Pathogenicity was dependent on engagement of activating FcgammaR, as FcRgamma-deficient mice were completely resistant to Ab-mediated arthritis. The arthritis induced with the IgG1 and IgG2b Ab was also inhibited by FcgammaRIII disruption, whereas arthritis mediated by the IgG2a Ab was not substantially affected. The arthritic response of the IgG1 and IgG2b isotypes, but not of the IgG2a Ab, was further enhanced in mice lacking the inhibitory FcgammaRIIB. These results demonstrate that single IgG anti-CII mAb can induce erosive arthritis and that IgG anti-CII Ab mediate arthritis by engagement of FcgammaR.
Nandakumar
Kutty Selva
KS
Medical Inflammation Research, Biomedical Center, Lund University, Lund, Sweden.
Andrén
Maria
M
Martinsson
Pernilla
P
Bajtner
Estelle
E
Hellström
Silvia
S
Holmdahl
Rikard
R
Kleinau
Sandra
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D024043:Collagen Type II / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000145:classification / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D017452:Receptors, IgG / Q000172:deficiency* / Q000235:genetics
D000911:Antibodies, Monoclonal; D024043:Collagen Type II; D007074:Immunoglobulin G; D017452:Receptors, IgG