Analysis of Lyn/CD22 double‐deficient B cells in vivo demonstrates Lyn‐ and CD22‐independent pathways affecting BCR regulation and B cell survival
Ferry H., Cockford TL., Silver K., Rust N., Goodnow CC., Cornall RJ.
AbstractB 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 (IgHEL). 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.