The activation and subsequent regulatory roles of Lyn and CD19 after B cell receptor ligation are independent.
The cell surface glycoprotein CD19 and the Src-related protein tyrosine kinase Lyn are key mediators of, respectively, positive and negative signaling in B cells. Despite the apparent opposition of their regulatory functions, a recent model of the biochemical events after B cell receptor (BCR) ligation intimately links the activation of Lyn and CD19. We examined the biochemical consequences of BCR ligation in mouse B cells lacking either Lyn or CD19 for evidence of interaction or codependence. In contrast to published results, we found CD19 phosphorylation after BCR ligation to be unaffected by the absence of Lyn, yet dependent on Src family protein tyrosine kinases as it was inhibited fully by PP2, an Src family-specific inhibitor. Consistent with normal CD19 phosphorylation in lyn(-/-) B cells, the recruitment of phosphoinositide-3 kinase to CD19 and the ability of CD19 to enhance both intracellular calcium flux and extracellular signal-regulated kinase 1/2 activation after coligation with the BCRs were intact in the absence of Lyn. Similarly, unique functions of Lyn were found to be independent of CD19. CD19(-/-) B cells were normal for increased Lyn kinase activity after BCR ligation, inhibition of BCR-mediated calcium flux after CD22 coligation, and inhibition of extracellular signal-regulated kinase phosporylation after FcgammaRIIB coligation. Collectively, these data show that the unique functions of Lyn do not require CD19 and that the signal amplification mediated by CD19 is independent of Lyn. We conclude that the roles of Lyn and CD19 after BCR ligation are independent and opposing, one being primarily inhibitory and the other stimulatory.
Xu
Yuekang
Y
Walter and Eliza Hall Institute of Medical Research, P. O. Royal Melbourne Hospital, Victoria, Australia.
Beavitt
Sarah-Jane E
SJ
Harder
Kenneth W
KW
Hibbs
Margaret L
ML
Tarlinton
David M
DM
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D018941:Antigens, CD19 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology; D016175:B-Lymphocyte Subsets / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D020013:Calcium Signaling / Q000235:genetics / Q000276:immunology; D015815:Cell Adhesion Molecules; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D037102:Lectins / Q000502:physiology; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism*; D017452:Receptors, IgG / Q000502:physiology; D051918:Sialic Acid Binding Ig-like Lectin 2; D013379:Substrate Specificity; D019061:src-Family Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*
D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; C080571:Fc gamma receptor IIB; D037102:Lectins; D008024:Ligands; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; D051918:Sialic Acid Binding Ig-like Lectin 2; D019869:Phosphatidylinositol 3-Kinases; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D020928:Mitogen-Activated Protein Kinases