Ikaros limits follicular B cell activation by regulating B cell receptor signaling pathways

Biochemical and Biophysical Research Communications
Beate HeizmannPhilippe Kastner

Abstract

The Ikaros transcription factor is essential for early B cell development, but its effect on mature B cells is debated. We show that Ikaros is required to limit the response of naive splenic B cells to B cell receptor signals. Ikaros deficient follicular B cells grow larger and enter cell cycle faster after anti-IgM stimulation. Unstimulated mutant B cells show deregulation of positive and negative regulators of signal transduction at the mRNA level, and constitutive phosphorylation of ERK, p38, SYK, BTK, AKT and LYN. Stimulation results in enhanced and prolonged ERK and p38 phosphorylation, followed by hyper-proliferation. Pharmacological inhibition of ERK and p38 abrogates the increased proliferative response of Ikaros deficient cells. These results suggest that Ikaros functions as a negative regulator of follicular B cell activation.

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Citations

Aug 11, 2020·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Serge MoffettRené Roy
Jun 12, 2018·The Journal of Clinical Investigation·David BoutboulSergio D Rosenzweig

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