Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 35, Issue 12, Pages 3655-3663Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/eji.200535247
Keywords
B lymphocytes; CD22; Lyn; lysozyme; transgene
Categories
Funding
- Wellcome Trust Funding Source: Medline
Ask authors/readers for more resources
B cell fate is determined by the strength of signals from the antigen receptor and from co-receptors that adjust the activation threshold and tune the B cell to its environment. These co-receptors have been broadly classified into inhibitory and enhancing groups, yet some, such as CD22, may have dual effects. CD22 recruits a variety of signal enhancers at the same time as Lyn-dependent phosphorylation leads to the binding of the inhibitory phosphatase SHP-1. To assess the relative importance of Lyn- and CD22-dependent and -independent pathways, we generated Lyn and CD22 single-deficient mice and Lyn/CD22 double-deficient mice expressing the MD4 immunoglobulin transgene against hen egg lysozyme (Ig(HEL)). This genetic approach has enabled us to compare the contributions of Lyn and CD22 to B cell development in vivo, independent of BCR specificity and in the presence and absence of self-antigen. Our results show that although the effects of Lyn are dominant in negative regulation of B cell hyperactivity, Lyn and CD22 have independent and additive effects on B cell survival. These findings emphasize the subtle nature of regulation at the BCR and the usefulness of genetic complementation to dissect common and parallel pathways.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available