title: Analysis of Lyn/CD22 double-deficient B cells in vivo demonstrates Lyn- and CD22-independent pathways affecting BCR regulation and B cell survival.
abstract: 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 (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.
authors.affiliation: Henry Wellcome Building of Molecular Physiology, Oxford, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Ferry
authors.forename: Tanya L
authors.initials: TL
authors.lastname: Crockford
authors.forename: Tanya L
authors.initials: TL
authors.lastname: Cockford
authors.forename: Karlee
authors.initials: K
authors.lastname: Silver
authors.forename: Nigel
authors.initials: N
authors.lastname: Rust
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Goodnow
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Cornall
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D007108:Immune Tolerance / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000235:genetics* / Q000502:physiology; D019061:src-Family Kinases / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology
chemical_list: C497868:Cd22 protein, mouse; D011947:Receptors, Antigen, B-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases