The Transcription Factor Gata-3 Regulates Il-4 Responses In B Cells

The GATA-3 transcription factor plays a central role in T helper type 2 development, but its role in B cells has not been well described, even though GATA-3 is present in naïve B cells. To study the role of GATA-3 in B cells, mice with a floxed Gata3 allele (Gata3fl/fl) mice were crossed to CD19-Cre transgenic mice, allowing B cell-specific deletion of GATA-3. B cell development was grossly normal in Gata3fl/fl CD19-Cre, but surprisingly, Gata3fl/fl CD19-Cre B cells showed a decreased ability to proliferate (in an IL-4 dose dependent manner) but an increased ability to produce IgG1 and IgE in response to anti-CD40 and/or IL-4 in vitro. These findings may reflect an interaction between GATA-3 and type 2 Ig-regulating transcription factors such as NF-kB or STAT6, because GATA-3 can modulate the activities of these factors in vitro. These findings demonstrate a critical yet surprising role for GATA-3 in the regulation of IL-4-mediated responses in B cells.