Characterization of the B Lymphocyte Populations in Lyn-Deficient Mice and the Role of Lyn in Signal Initiation and Down-Regulation

• Published in: Immunity (Cambridge, Mass.) Vol. 7; no. 1; pp. 69 - 81
• Main Authors: Chan, Vivien W.F, Meng, Fanying, Soriano, Philippe, DeFranco, Anthony L, Lowell, Clifford A
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.1997
• Subjects: Aging - genetics; Aging - immunology; Animals; Antibodies, Anti-Idiotypic - metabolism; Antigens, CD - biosynthesis; Autoantibodies - metabolism; B-Lymphocytes - cytology; B-Lymphocytes - enzymology; B-Lymphocytes - metabolism; B7-2 Antigen; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Chickens; Down-Regulation; Lipopolysaccharides - pharmacology; Membrane Glycoproteins - biosynthesis; Mice; Phenotype; Phosphorylation; Pseudogenes; Receptors, IgG - metabolism; Signal Transduction; src-Family Kinases - deficiency; src-Family Kinases - genetics; src-Family Kinases - metabolism; Surface Properties; Tyrosine - metabolism
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/S1074-7613(00)80511-7

Lyn-deficient mice were generated to analyze the role of Lyn in B cell antigen receptor (BCR) signaling. These mice had a reduced number of peripheral B cells with a greater proportion of immature cells and a higher than normal turnover rate. Aged lyn −/− mice developed splenomegaly, produced autoantibodies, and had an expanded population of B lymphoblasts of the B1 lineage. Splenic B cells from young lyn −/− mice initiated early BCR signaling events, although in a delayed fashion. Unexpectedly, lyn −/− B cells exhibited an enhanced MAP kinase activation and an increased proliferative response to BCR engagement. Stimulation of lyn −/− B cells with intact and F(ab′) 2 anti-IgM revealed defects in at least two mechanisms that negatively regulate BCR signaling, one of which involves FcγRIIb1.