Altered Development of Collagen Induced Arthritis in T Cell Receptor V_β Congenic B10.RIII Mice

Abstract

Analysis of the mouse T cell receptor (TCR) V_β genome has revealed the existence of two distinct genotypes which bear deletions of certain V_β genes. Mice bearing the V^a_β genotype lack approximately 50% of the V_β genome while V^c_β mice lack 70% of the known V_β genes. Studies of the experimental model collagen induced arthritis (CIA) have indirectly suggested that the presence of truncated V_β genotypes may influence susceptibility to this autoimmune disease. In order to confirm the influence of V^a_β and V^c_β genotypes on CIA, we derived mice congenic for the known V_β haplotypes in the CIA susceptible B10.RIII (H-2^r) background. Flow cytometric analysis of splenic lymphocytes revealed normal T cell levels in both B10.RIII-V_β congenic lines. Expectedly, a generalized increase in the expression of some non-deleted V_β genes was detected. In addition, the mice were immunized with porcine type II collagen and monitored for CIA. B10.RIII-V^a_β 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^c_β mice showed a marked decrease in arthritis incidence versus B10.RIII and the severity of CIA in arthritic mice was also significantly lower (p < 0.01). Thus, in the B10.RIII strain, the presence of truncated TCR V_β genotypes alters the development of CIA. These findings may shed light on the influence of TCR genotypes in the induction and development of human rheumatoid arthritis.

Key Words:

• CIA, collagen induced arthritis
• CII, native type II collagen