| First Author | Macias-Garcia A | Year | 2016 |
| Journal | J Biol Chem | Volume | 291 |
| Issue | 17 | Pages | 9073-86 |
| PubMed ID | 26841869 | Mgi Jnum | J:233727 |
| Mgi Id | MGI:5787899 | Doi | 10.1074/jbc.M115.704239 |
| Citation | Macias-Garcia A, et al. (2016) Ikaros Is a Negative Regulator of B1 Cell Development and Function. J Biol Chem 291(17):9073-86 |
| abstractText | 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. |
