Genetic evidence for Lyn as a negative regulator of IL-4 signaling
- Author(s)
- Janas, ML; Hodgkin, P; Hibbs, M; Tarlinton, D;
- Details
- Publication Year 1999-10-15,Volume 163,Issue #8,Page 4192-4198
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- IL-4 has multiple effects on B lymphocytes, many of which are concentration dependent. This is particularly so for Ig isotype switching, where different thresholds of IL-4 stimulation are needed to induce switching from IgM to either IgG1 or IgE, In this report we describe a critical role for the tyrosine kinase Lyn in setting IL-4 signaling thresholds in mouse B lymphocytes. Upon CD40 ligand stimulation of lyn(-/-) B cells, 10-fold less IL-4 was required to induce switching from IgM to IgG1 and IgE and an increased proportion of B cells isotype switched at each IL-4 concentration, These in vitro results correlate with the in vivo findings that in lyn(-/-) mice, IgG1 Ab-forming cells develop prematurely in ontogeny and that adult lyn(-/-) mice have an abnormally high proportion of IgG1-expressing B cells in their spleens. Adult lyn(-/-) mice also have significantly higher levels of IgE in their serum. These results identify Lyn as a molecule involved in modulating the IL-4 signal in B cells and provide insights into its regulation and how a B cell signaling imbalance may contribute to atopy.
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Keywords
- PROTEIN-TYROSINE KINASES; B-CELLS; DEFICIENT MICE; AUTOIMMUNE-DISEASE; INTERLEUKIN-4 RECEPTOR; STIMULATING FACTOR; IN-VITRO; IDENTIFICATION; DIVISION; PHOSPHORYLATION
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Creation Date: 1999-10-15 12:00:00