Induction of experimental arthritis in BALB/c mice by inclusion of a foreign protein in the collagen inoculum.

The susceptibility of mice to collagen-induced arthritis (CIA) has, among other things, been linked to the major histocompatibility complex class II genes as well as other genes. This study was designed to examine the possibilities to establish CIA in low susceptible I-Ad (Balb/C) mice. Balb/C mice were immunized twice with bovine type II collagen (BCII) in complete Freund's adjuvant (CFA) containing the amount of Mycobacterium tuberculosis needed to induce CIA in low susceptible I-Ab (C57BL/6) mice. Some mice received the conceivable arthritogenic inoculum mixed with ovalbumin (OVA). Clinical arthritis was monitored. Antibody activity and T-cell reactivity to BCII were determined. Unexpectedly, only mice that were immunized with the BCII-OVA mixture developed arthritis. Combining BCII with another foreign protein, keyhole limpet hemocyanin, but not the self-protein mouse serum albumin, also triggered arthritis. Prior to the appearance of arthritis the serum levels of IgG autoantibodies to BCII were higher in the coimmunized mice than in the mice that were immunized with BCII alone. Yet, splenocytes stimulated in vitro with BCII did not proliferate or produce interferon-gamma. Immunization of Balb/c mice with an emulsion-containing CFA and BCII mixed with a foreign body, but not a self-protein, elevates the level of circulating autoantibodies to CII and subsequently induces arthritis.