title: Multiple defects in the immune system of Lyn-deficient mice, culminating in autoimmune disease.
abstract: Mice homozygous for a disruption at the Lyn locus display abnormalities associated with the B lymphocyte lineage and in mast cell function. Despite reduced numbers of recirculating B lymphocytes, Lyn-/- mice are immunoglobulin M (IgM) hyperglobulinemic. Immune responses to T-independent and T-dependent antigens are affected. Lyn-/- mice fail to mediate an allergic response to IgE cross-linking, indicating that activation of LYN plays an indispensable role in Fc epsilon RI signaling. Lyn-/- mice have circulating autoreactive antibodies, and many show severe glomerulonephritis caused by the deposition of IgG immune complexes in the kidney, a pathology reminiscent of systemic lupus erythematosus. Collectively, these results implicate LYN as having an indispensable role in immunoglobulin-mediated signaling, particularly in establishing B cell tolerance.
authors.affiliation: Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Royal Melbourne Hospital, Victoria, Australia.
authors.forename: M L
authors.initials: ML
authors.lastname: Hibbs
authors.forename: D M
authors.initials: DM
authors.lastname: Tarlinton
authors.forename: J
authors.initials: J
authors.lastname: Armes
authors.forename: D
authors.initials: D
authors.lastname: Grail
authors.forename: G
authors.initials: G
authors.lastname: Hodgson
authors.forename: R
authors.initials: R
authors.lastname: Maglitto
authors.forename: S A
authors.initials: SA
authors.lastname: Stacker
authors.forename: A R
authors.initials: AR
authors.lastname: Dunn
mesh_terms: D000707:Anaphylaxis / Q000276:immunology; D000818:Animals; D000917:Antibody Formation; D001327:Autoimmune Diseases / Q000209:etiology / Q000235:genetics*; D001402:B-Lymphocytes / Q000473:pathology*; D001483:Base Sequence; D005921:Glomerulonephritis / Q000235:genetics / Q000276:immunology; D007107:Immune System / Q000002:abnormalities*; D007073:Immunoglobulin E / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood; D007668:Kidney / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D019061:src-Family Kinases / Q000172:deficiency* / Q000235:genetics
chemical_list: D007075:Immunoglobulin M; D007073:Immunoglobulin E; D019061:src-Family Kinases