Fiche publication
Date publication
avril 2016
Journal
The Journal of biological chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHAN Susan
,
Dr KASTNER Philippe
,
Pr MULLER Sylviane
,
Dr HEIZMANN Beate
Tous les auteurs :
Macias-Garcia A, Heizmann B, Sellars M, Marchal P, Dali H, Pasquali JL, Muller S, Kastner P, Chan S
Lien Pubmed
Résumé
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.
Mots clés
Animals, Autoantibodies, immunology, B-Lymphocyte Subsets, immunology, Bone Marrow Cells, immunology, Ikaros Transcription Factor, genetics, Immunoglobulin M, immunology, Mice, Mice, Knockout, Precursor Cells, B-Lymphoid, immunology, Toll-Like Receptor 4, genetics
Référence
J. Biol. Chem.. 2016 Apr;291(17):9073-86
