Paul H. Wooley

Passive Transfer of Arthritis to Mice by Injection of Human Anti-Type II Collagen Antibody

The serum IgG fraction from a patient with seronegative rheumatoid-like arthritis which contained a high anti-type II collagen antibody titer was injected intravenously into mice susceptible to type II collagen-induced arthritis. A mild, transient, inflammatory arthritis was observed in 20 to 25% of the animals, whereas histologic signs of disease were evident in most of the injected mice. Purified human anti-type II collagen immunoglobulin injected into the knee joints of mice was also shown to induce a transient, inflammatory arthritis. Radiolabeled human anti-type II collagen IgG was shown to accumulate in the peripheral joints of mice, and the specificity of the antibody was shown to be similar to the specificity of anticollagen antibody eluted from the joints of mice with collagen-induced arthritis.

Major histocompatibility complex genes and their role in autoimmune and infectious diseases

Publisher Summary This chapter discusses the developments leading to the establishment of the major histocompatibility complex (H-2 and HLA) and the important contributions made by the mouse system toward better understanding of the human disease. The golden age of immunogenetic studies in mice arrived when it was found that genes that were originally thought to be of relevance only in transplantation and histocompatibility also influenced immune responses to numerous antigens, susceptibility to several diseases, and the killing of virus infected cells. Fortunately, for the immunologists, the transplant geneticists had already produced numerous stocks of inbred mice that could be immediately used for studies on immune response and disease association. Several decades of studies on the mouse histocompatibility genes (H-2 genes) enabled rapid progress on the human histocompatibility studies leading to the identification and characterization of the HLA system. The striking homology between the mouse H-2 system and the human HLA system in terms of genetics, serology, structure, and function further propelled the mouse as the ideal animal model to study human immunogenetics. The chapter also explores a number of disease models, such as murine models, where immunogenetic studies have advanced the research into the corresponding human disease. There are several excellent murine models of human diseases with HLA associations, and several murine models of human disease where HLA involvement has not been significantly investigated.