| First Author | Schwickert TA | Year | 2019 |
| Journal | Nat Immunol | Volume | 20 |
| Issue | 11 | Pages | 1517-1529 |
| PubMed ID | 31591571 | Mgi Jnum | J:282532 |
| Mgi Id | MGI:6381195 | Doi | 10.1038/s41590-019-0490-2 |
| Citation | Schwickert TA, et al. (2019) Ikaros prevents autoimmunity by controlling anergy and Toll-like receptor signaling in B cells. Nat Immunol 20(11):1517-1529 |
| abstractText | The establishment of a diverse B cell antigen receptor (BCR) repertoire by V(D)J recombination also generates autoreactive B cells. Anergy is one tolerance mechanism; it renders autoreactive B cells insensitive to stimulation by self-antigen, whereas Toll-like receptor (TLR) signaling can reactivate anergic B cells. Here, we describe a critical role of the transcription factor Ikaros in controlling BCR anergy and TLR signaling. Mice with specific deletion of Ikaros in mature B cells developed systemic autoimmunity. Ikaros regulated many anergy-associated genes, including Zfp318, which is implicated in the attenuation of BCR responsiveness by promoting immunoglobulin D expression in anergic B cells. TLR signaling was hyperactive in Ikaros-deficient B cells, which failed to upregulate feedback inhibitors of the MyD88-nuclear factor kappaB signaling pathway. Systemic inflammation was lost on expression of a non-self-reactive BCR or loss of MyD88 in Ikaros-deficient B cells. Thus, Ikaros acts as a guardian preventing autoimmunity by promoting BCR anergy and restraining TLR signaling. |
