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Published on: October 4, 2018
A role in B cell activation for CD22 and the protein tyrosine phosphatase SHP
G M Doody1, L B Justement, C C Delibrias
1Wellcome Trust Immunology Unit, Department of Medicine, University of Cambridge, School of Clinical Medicine, UK.
Insights
CD22 protein on B cells acts as a molecular switch. It regulates B cell activation by interacting with SHP, a phosphatase, influencing immune responses.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- CD22 is a protein associated with membrane immunoglobulin (mIg) on B cells.
- Upon mIg ligation, CD22 undergoes tyrosine phosphorylation.
Purpose of the Study:
- To investigate the role of CD22 in regulating B cell signaling.
- To understand how CD22 influences the activation threshold of B cells.
Main Methods:
- Studying CD22 phosphorylation and its interaction with SHP (a protein tyrosine phosphatase).
- Analyzing the effect of CD22 ligation on mIg-mediated B cell activation.
- Investigating CD22 localization in secondary lymphoid organs.
Main Results:
- Tyrosine-phosphorylated CD22 binds and activates SHP, which negatively regulates mIg signaling.
- Preventing CD22 coaggregation with mIg reduces the B cell activation threshold by 100-fold.
- CD22 may be sequestered from mIg by T cell counterreceptors in lymphoid organs.
Conclusions:
- CD22 functions as a molecular switch for SHP, modulating B cell signaling.
- CD22 may direct mIg signaling to T cell-rich areas in secondary lymphoid organs.
Abstract:
CD22 is a membrane immunoglobulin (mIg)-associated protein of B cells. CD22 is tyrosine-phosphorylated when mIg is ligated. Tyrosine-phosphorylated CD22 binds and activates SHP, a protein tyrosine phosphatase known to negatively regulate signaling through mIg. Ligation of CD22 to prevent its coaggregation with mIg lowers the threshold at which mIg activates the B cell by a factor of 100. In secondary lymphoid organs, CD22 may be sequestered away from mIg through interactions with counterreceptors on T cells. Thus, CD22 is a molecular switch for SHP that may bias mIg signaling to anatomic sites rich in T cells.
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