Abrogation of autoimmune disease in Lyn-deficient mice by the deletion of IL-5 receptor alpha chain gene.
Lyn, the src-family protein tyrosine kinase, plays a crucial role in the regulation of B cell antigen receptor (BCR)- and IL-5-receptor (IL-5R)-mediated signaling. Lyn-deficient mice have been reported to exhibit an increase in B-1 cell numbers, splenomegaly and accumulation of lymphoblast-like cells in the spleen with age, resulting in hyperimmunoglobulinemia and glomerulonephritis caused by the deposition of autoantibody complexes. To elucidate the role of IL-5 in B-1 cell activation, autoantibody production and autoimmune diseases, Lyn-deficient mice were crossed with IL-5Ralpha chain (IL-5Ralpha)-deficient mice and generated Lyn- and IL-5Ralpha-deficient (DKO) mice. In contrast to Lyn-deficient mice, DKO mice showed significantly reduced splenomegaly and lymphoadenopathy and reduced B-1 cell number in the peritoneal cavity. DKO mice also secreted low levels of IgM and IgG autoantibodies. Biochemical and histological analyses revealed that DKO mice showed milder pathogenesis of autoimmune-like disorders than Lyn-deficient mice. These results suggest involvement of IL-5 in enhanced B-1 cell activation, autoantibody production, and development of autoimmune disease in Lyn-deficient mice.
Moon
Byoung-gon
BG
Division of Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Takaki
Satoshi
S
Nishizumi
Hirofumi
H
Yamamoto
Tadashi
T
Takatsu
Kiyoshi
K
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D017353:Gene Deletion; D006651:Histocytochemistry; D007132:Immunoglobulin Isotypes; D007668:Kidney / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000473:pathology; D008206:Lymphatic Diseases / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology*; D053649:Receptors, Interleukin-5; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology / Q000473:pathology; D019061:src-Family Kinases / Q000172:deficiency* / Q000235:genetics / Q000276:immunology
D001323:Autoantibodies; D007132:Immunoglobulin Isotypes; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases