1. Ikaros Is a Negative Regulator of B1 Cell Development and Function.
- Author
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Macias-Garcia A, Heizmann B, Sellars M, Marchal P, Dali H, Pasquali JL, Muller S, Kastner P, and Chan S
- Subjects
- Animals, Ikaros Transcription Factor genetics, Mice, Mice, Knockout, Toll-Like Receptor 4 genetics, Toll-Like Receptor 4 immunology, Autoantibodies immunology, B-Lymphocyte Subsets immunology, Bone Marrow Cells immunology, Ikaros Transcription Factor immunology, Immunoglobulin M immunology, Precursor Cells, B-Lymphoid immunology
- 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 ∼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., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)
- Published
- 2016
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