Negative regulation of B cell receptor-mediated signaling in B-1 cells through CD5 and Ly49 co-receptors via Lyn kinase activity.
CD5(+) B-1 cells are known to be unresponsive to B cell receptor (BCR)-mediated growth signals but instead undergo apoptosis. However, the B-1 cells from Lyn kinase-deficient (Lyn-/-) mice exhibited an enhanced proliferative response upon BCR cross-linking. It has been reported that BCR-mediated signaling in B-1 cells is negatively regulated by signals from CD22, CD5 and CD72 co-receptors, and that Lyn kinase plays a crucial role in tyrosine phosphorylation of immunoreceptor tyrosine-based inhibitory motifs on the CD22 and CD72, which recruits SHP-1 to the BCR complex. We found that Lyn kinase is also essential for the tyrosine phosphorylation of CD5 and subsequent recruitment of SHP-1 in B-1 cells upon cross-linking of BCR. Moreover, a distinct subpopulation of B-1 cells was found to express cell surface Ly49, which is known as a MHC class I-binding negative regulatory receptor on NK cells. Ly49 was rapidly tyrosine phosphorylated upon cross-linking of BCR and SHP-1 was found to recruit to the phosphorylated Ly49. Addition of F(ab')(2) fragments of anti-Ly49 antibodies partially blocked negative signals in B-1 cells. Thus two co-receptors, CD5 and Ly49, which are unique to B-1 cells, play a role in the regulation of B-1 cell activation. These results indicate that BCR-mediated signals in B-1 cells are strictly and negatively regulated through multiple pathways, that are dependent on Lyn kinase activity.
Ochi
H
H
Department of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
Watanabe
T
T
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology; D000950:Antigens, Ly; D001402:B-Lymphocytes / Q000502:physiology*; D018956:CD5 Antigens / Q000502:physiology*; D015815:Cell Adhesion Molecules; D037102:Lectins; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D055630:Receptors, NK Cell Lectin-Like; D051918:Sialic Acid Binding Ig-like Lectin 2; D015398:Signal Transduction; D019061:src-Family Kinases / Q000502:physiology*
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000950:Antigens, Ly; D018956:CD5 Antigens; C064228:CD72 protein, human; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D037102:Lectins; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; D055630:Receptors, NK Cell Lectin-Like; D051918:Sialic Acid Binding Ig-like Lectin 2; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases