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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.

Domains

Immunology

Dates and versions

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

Identifiers

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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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