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

Beate Heizmann (1, 2) , Maclean Sellars , Beatriz Alejandra Macias Garcia (1) , Susan Chan (1, 2) , Philippe Kastner (1, 2)

1 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
2 IGBMC - Institut de génétique et biologie moléculaire et cellulaire

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.

Domaines: Immunologie

Beate Heizmann, Maclean Sellars, Beatriz Alejandra Macias Garcia, Susan Chan, Philippe Kastner. Ikaros limits follicular B cell activation by regulating B cell receptor signaling pathways. Biochemical and biophysical research communications, 2016, 470 (3), pp.714-720. ⟨10.1016/j.bbrc.2016.01.060⟩. ⟨hal-03680460⟩