ALTERED DEVELOPMENT OF COLLAGEN-INDUCED ARTHRITIS IN T-CELL RECEPTOR V-BETA CONGENIC B10.RIII MICE

Analysis of the mouse T cell receptor (TCR) V-beta genome has revealed the existence of two distinct genotypes which bear deletions of certa in V-beta genes. Mice bearing the V-beta(a) genotype lack approximatel y 50% of the V-beta genome while V-beta(c) mice lack 70% of the known V-beta genes. Studies of the experimental model collagen induced arthr itis (CIA) have indirectly suggested that the presence of truncated V- beta genotypes may influence susceptibility to this autoimmune disease . In order to confirm the influence of V-beta(a) and V-beta(c) genotyp es on CIA, we derived mice congenic for the known V-beta haplotypes in the CIA susceptible B10.RIII (H-2(r)) background. Flow cytometric ana lysis of splenic lymphocytes revealed normal T cell levels in both B10 .RIII-V-beta congenic lines. Expectedly, a generalized increase in the expression of some non-deleted V-beta genes was detected. In addition , the mice were immunized with porcine type II collagen and monitored for CIA. B10.RIII-V-beta(a) mice showed little difference in arthritis incidence or severity versus B10.RIII, but a significant delay in the onset of CIA was seen. In contrast, B10.RIII-V-beta(c) mice showed a marked decrease in arthritis incidence versus B10.RIII and the severit y of CIA in arthritic mice was also significantly lower (p < 0.01). Th us, in the B10.RIII strain, the presence of truncated TCR V-beta genot ypes alters the development of CIA. These findings may shed light on t he influence of TCR genotypes in the induction and development of huma n rheumatoid arthritis.