| First Author | Janas ML | Year | 1999 |
| Journal | J Immunol | Volume | 163 |
| Issue | 8 | Pages | 4192-8 |
| PubMed ID | 10510355 | Mgi Jnum | J:106741 |
| Mgi Id | MGI:3619318 | Doi | 10.4049/jimmunol.163.8.4192 |
| Citation | Janas ML, et al. (1999) Genetic evidence for Lyn as a negative regulator of IL-4 signaling. J Immunol 163(8):4192-8 |
| abstractText | 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. |
