Analysis of Lyn/CD22 double-deficient B cells in vivo demonstrates Lyn- and CD22-independent pathways affecting BCR regulation and B cell survival

Date

2005

Authors

Ferry, Helen
Cockford, Tanya L
Silver, Karlee
Rust, Nigel
Goodnow, Christopher
Cornall, Richard J

Journal Title

Journal ISSN

Volume Title

Publisher

Wiley-VCH Verlag GMBH

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.

Description

Keywords

Keywords: B lymphocyte receptor; CD22 antigen; egg protein; immunoglobulin; lysozyme; protein kinase Lyn; animal cell; animal experiment; article; autoimmunity; B lymphocyte; B lymphocyte differentiation; cell survival; controlled study; enzyme phosphorylation; fem B lymphocytes; CD22; Lyn; Lysozyme; Transgene

Citation

Source

European Journal of Immunology

Type

Journal article

Book Title

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Restricted until

2037-12-31