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Regulation of B Cell Antigen Receptor Signaling by the Lyn/CD22/SHP1 Pathway

1999; Springer Science+Business Media; Linguagem: Inglês

10.1007/978-3-642-58537-1_5

2196-9965

Richard J. Cornall, Christopher C. Goodnow, Jason G. Cyster,

Immunotherapy and Immune Responses

In a resting cell, the B cell antigen receptor (BCR) is in an equilibrium of phosphorylated and unphosphorylated states that is tuned by counteracting kinases and phosphatases. Contributing to this tuning are transmembrane molecules (e.g., CD19/CD21, CD22, FcγRIIBl) whose cytoplasmic domains act as necessary docks for the activated kinases and phosphatases. When antigens cluster and increase the local density of BCRs, the equilibrium state is lost, tyrosine phosphorylation of BCR-associated molecules CD79 α/β, Syk kinase, CD22, and CD 19 is markedly increased and there is recruitment and activation of further signaling enzymes leading to multiple downstream changes in the cell. The magnitude and duration of the activating signal continues to be influenced, however, by the balance of kinase and phosphatase activity and the availability of transmembrane docking molecules. In this review, recent experiments will be discussed that have shown how BCR-induced activation of the src family kinase Lyn initiates the constitutive and antigen-induced feedback inhibition of the BCR through the phosphorylation of CD22 and recruitment of the phosphatase SHP1 to the CD22/BCR complex.