Normal B-1 cell development but defective BCR signaling in Lck-/- mice.
Mature B cells are grouped into two major subsets, B-1 and B-2, believed to derive from separate lineages. We have recently shown that B-1 cells, which are characterized by CD5 surface expression, specifically exhibit significant levels of the tyrosine kinase Lck in man. Here we show that also in mice Lck expression is restricted to B-1 cells and address the potential role of Lck in B-1 cell development and activation. Using as a model an Lck-/- mouse, we show that, while dispensable for B-1 cell development, Lck is required for full and sustained activation of the tyrosine phosphorylation and MAP kinase cascades triggered by the BCR in CD5+, B-1 cells. The data suggest a potential role for Lck in the achievement of the higher activation threshold required for productive BCR signaling in B-1 as compared to B-2 cells.
Ulivieri
Cristina
C
Department of Evolutionary Biology, University of Siena, Siena, Italy.
Valensin
Silvia
S
Majolini
M Bernardetta
MB
Matthews
R James
RJ
Baldari
Cosima T
CT
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D018956:CD5 Antigens / Q000032:analysis; D008213:Lymphocyte Activation / Q000502:physiology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D010529:Peritoneal Cavity / Q000166:cytology; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000172:deficiency; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018631:ras Proteins / Q000502:physiology
D018956:CD5 Antigens; D011947:Receptors, Antigen, B-Cell; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D010744:Phosphoric Monoester Hydrolases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D018631:ras Proteins