Depletion of Lyn kinase from the BCR complex and inhibition of B cell activation by excess CD21 ligation.
The human and murine CD21 gene products have been functionally linked to B cell activation by the co-ligation of the BCR and the CD21/CD19/CD81 complexes. Binding of low levels of antigen complexed to the complement ligand(s) for CD21 enhances B cell activation compared to the stimulation caused by antigen alone. Mice lacking functional CD21 predispose to autoimmune responses suggesting that this receptor may also play a negative role: thus in the presence of excess complement-bearing immune complexes, B cell antigen-specific activation may be inhibited. This possibility was investigated using intracellular calcium elicitation analyses to follow BCR-mediated activation. Ligation of the BCR and limiting quantities of the CD21 receptor demonstrated the expected enhanced cellular response compared to BCR ligation alone: CD21 ligation alone demonstrated no alteration in calcium flux. However, co-ligation of the BCR with excess CD21 binding resulted in the elimination of the calcium response, suggesting that CD21 ligation was down-modulating the BCR response. Immunoprecipitation of kinases associated with the BCR and CD21/CD19/CD81 complexes demonstrated that Lyn is preferentially depleted from the BCR complex following excess binding of CD21. Localization of other kinases integral for B cell activation is not altered. These data suggest that excess CD21 ligand binding can negatively impact B cell activation by sequestering Lyn kinase away from the BCR complex.
Chakravarty
Leena
L
Division of Cell Biology and Immunology, Department of Pathology, University of Utah, School of Medicine, 50 N. Medical Drive, Salt Lake City, UT 84132, USA.
Zabel
Mark D
MD
Weis
Janis J
JJ
Weis
John H
JH
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D007075:Immunoglobulin M / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D051381:Rats; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D017464:Receptors, Complement 3d / Q000502:physiology*; D019061:src-Family Kinases / Q000502:physiology*
D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D017464:Receptors, Complement 3d; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases