Interactions between H-2 and background genes modulate collagen induced arthritis in high (HI) and low (LI) antibody...

The experimental arthritis (collagen induced arthritis, CIA) induced in mice by heterologous collagen of type II is mainly restricted to the H-2q or H-2r haplotypes. However, data including ours, strongly suggest that CIA is also under non MHC polygenic control. This point has been studied in new sub-strains of high (HI) and low (LI) Biozzi mice made congenic for H-2q and H-2s: the original Biozzi lines HI/H-2q and LI/H-2s and the new HI/H-2s, LI/H-2q congenic mice. 80% of the HI/H-2q mice develop severe chronic inflammatory symptoms with joint deformation and swelling soon after induction of the disease, while 60% of LI/H-2q counterpart develop at a later stage, deformation of joints with no or mild swelling. In the H-2s haplotype, considered to be non or weakly permissive to CIA, 40% of HI/H-2s have strong CIA symptoms; the LI/H-2s being totally refractory. Thus, if MHC products play a crucial role in selecting the arthritogenic epitope of CII; non H-2 genes strongly modulate the severity of experimental arthritis.