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Significance The protein kinase fms-like tyrosine kinase 3 receptor (Flt3) has an important role during early B-cell development. Recent reports have shown that Flt3 is reexpressed on peripheral B cells during activation, however the function for Flt3 during B-cell activation is poorly understood. The present study describes a role for Flt3 during B-cell activation and antibody production. We show that Flt3 is reexpressed on activated germinal center B cells and that lack of functional Flt3 signaling in peripheral B cells results in a specific deficiency in production of the antibody subclass IgG1. Mechanistic studies indicate that Flt3 synergizes with the IL-4 receptor to promote proper activation of Stat6 and class switch to IgG1. This study provides evidence for a previously unknown function for Flt3 during peripheral B-cell activation.

Murine germinal center B cells require functional Fms-like tyrosine kinase 3 signaling for IgG1 class-switch recombination