Genetic factors predisposing to B-CLL and to autoimmune disease in spontaneous murine model.
The frequent occurrence of autoimmune diseases in patients with B cell chronic lymphocytic leukemia (B-CLL) or in their family members suggests the involvement of related predisposing genetic factors in the two distinct disorders. Because the majority of B-CLL is of CD5 B cell type, and because the majority of CD5 B cells produces polyreactive autoantibodies, certain regulatory abnormalities in the proliferation and differentiation of CD5 B cells appear to be involved in B-CLL and autoimmune disease, respectively. In studies using MHC(H-2)-congenic New Zealand mouse strains, NZB(H-2d), NZW(H-2z) and NZB x NZW F1(H-2d/z), we found that while H-2d/z heterozygosity acts as one genetic predisposing element for autoimmune disease, by providing the element for abnormal differentiation of CD5 B cells, the H-2z/z homozygosity serves as one predisposition for B-CLL, by promoting the abnormal proliferation of CD5 B cells. Another non-MHC-linked genes were also involved in the aberrant proliferation of CD5 B cells, as determined by microsatellite DNA analysis. Among these, there was a single dominant NZW locus located on chromosome 6, closely linked to the locus for TNF receptor p55. Hence our mouse model provides an appropriate tool for studying the relationship between genetic factors predisposing to B-CLL and autoimmune diseases.
Hirose
S
S
Department of Pathology, Juntendo University School of Medicine, Tokyo, Japan.
Hamano
Y
Y
Shirai
T
T
D000375:Aging / Q000276:immunology; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology; D018956:CD5 Antigens / Q000276:immunology; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005434:Flow Cytometry; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D005802:Genes, MHC Class II; D006183:H-2 Antigens / Q000276:immunology; D006579:Heterozygote; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains
D001323:Autoantibodies; D018956:CD5 Antigens; D006183:H-2 Antigens