Characterization of the B lymphocyte populations in Lyn-deficient mice and the role of Lyn in signal initiation and down-regulation.
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 Fc gammaRIIb1.
Chan
V W
VW
Department of Biochemistry and Biophysics, George Williams Hooper Foundation, University of California, San Francisco 94143, USA.
Meng
F
F
Soriano
P
P
DeFranco
A L
AL
Lowell
C A
CA
D000375:Aging / Q000235:genetics / Q000276:immunology; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000378:metabolism; D015703:Antigens, CD / Q000096:biosynthesis; D001323:Autoantibodies / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D051940:B7-2 Antigen; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002645:Chickens; D015536:Down-Regulation; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D010641:Phenotype; D010766:Phosphorylation; D011544:Pseudogenes; D017452:Receptors, IgG / Q000378:metabolism; D015398:Signal Transduction; D013499:Surface Properties; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D000888:Antibodies, Anti-Idiotypic; D015703:Antigens, CD; D001323:Autoantibodies; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D017452:Receptors, IgG; C044203:anti-IgM; D014443:Tyrosine; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases