title: Abrogation of autoimmune disease in Lyn-deficient mice by the mutation of the Btk gene.
abstract: Lyn and Btk play a critical role in B cell development and intracellular signaling. Lyn-deficient mice exhibit splenomegaly, elevated serum levels of IgM, production of autoantibody and glomerulonephritis with age. On the other hand, xid mice, which carry a point mutation in the btk gene, show a decrease in numbers of peripheral mature B cells, reduced serum levels of IgM and IgG3, disappearance of CD5+ B-1 cells, and low proliferative response to anti-IgM or LPS stimulation in vitro. In order to investigate the interaction between Lyn and Btk during B cell development, we established lyn-deficient xid mice. Lyn-deficient xid mice exhibited greatly reduced numbers of peripheral mature B cells, disappearance of CD5+ B-1 cells, markedly reduced serum levels of IgM and IgG3, low proliferative response to anti-IgM or lipopolysaccharide stimulation and no evidence for autoimmune disease. In addition, splenomegaly in lyn-deficient mice, which was mainly due to the accumulation of Mac-1+, cytoplasmic IgM+ lymphoblast-like cells, was also diminished in lyn-deficient xid mice. Thus, immunological abnormalities found in lyn-deficient mice were strongly affected by the absence of Btk. The present results suggest that the autoimmune symptoms in lyn-deficient mice may be caused by not only the abnormal response of B-2 cells but also that of B-1 cells, and that the interaction between Lyn and Btk is partly in tandem at the signaling pathway in B cells.
authors.affiliation: Department of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Takeshita
authors.forename: I
authors.initials: I
authors.lastname: Taniuchi
authors.forename: J
authors.initials: J
authors.lastname: Kato
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007075:Immunoglobulin M / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000502:physiology; D016177:Macrophage-1 Antigen / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010529:Peritoneal Cavity / Q000166:cytology; D017354:Point Mutation; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology; D019061:src-Family Kinases / Q000172:deficiency* / Q000235:genetics / Q000276:immunology
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016177:Macrophage-1 Antigen; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse; D019061:src-Family Kinases