Genetic evidence for Lyn as a negative regulator of IL-4 signaling

ML Janas, P Hodgkin, M Hibbs… - The Journal of …, 1999 - journals.aai.org
The Journal of Immunology, 1999journals.aai.org
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 …
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.
journals.aai.org