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Journal Articles Journal of Biological Chemistry Year : 2016

Ikaros Is a Negative Regulator of B1 Cell Development and Function

Abstract

B1 B cells secrete most of the circulating natural antibodies and are considered key effector cells of the innate immune response. However, B1 cell-associated antibodies often cross-react with self-antigens, which leads to autoimmunity, and B1 cells have been implicated in cancer. How B1 cell activity is regulated remains unclear. We show that the Ikaros transcription factor is a major negative regulator of B1 cell development and function. Using conditional knock-out mouse models to delete Ikaros at different locations, we show that Ikaros-deficient mice exhibit specific and significant increases in splenic and bone marrow B1 cell numbers, and that the B1 progenitor cell pool is increased approximately 10-fold in the bone marrow. Ikaros-null B1 cells resemble WT B1 cells at the molecular and cellular levels, but show a down-regulation of signaling components important for inhibiting proliferation and immunoglobulin production. Ikaros-null B1 cells hyper-react to TLR4 stimulation and secrete high amounts of IgM autoantibodies. These results indicate that Ikaros is required to limit B1 cell homeostasis in the adult.

Dates and versions

hal-03680465 , version 1 (27-05-2022)

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Beatriz Alejandra Macias Garcia, Beate Heizmann, Maclean Sellars, Patricia Marchal, Hayet Safidine Dali, et al.. Ikaros Is a Negative Regulator of B1 Cell Development and Function. Journal of Biological Chemistry, 2016, 291 (17), pp.9073-86. ⟨10.1074/jbc.M115.704239⟩. ⟨hal-03680465⟩
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