| First Author | Poe JC | Year | 2014 |
| Journal | J Exp Med | Volume | 211 |
| Issue | 1 | Pages | 57-69 |
| PubMed ID | 24344237 | Mgi Jnum | J:208364 |
| Mgi Id | MGI:5562977 | Doi | 10.1084/jem.20130648 |
| Citation | Poe JC, et al. (2014) EndoU is a novel regulator of AICD during peripheral B cell selection. J Exp Med 211(1):57-69 |
| abstractText | Balanced transmembrane signals maintain a competent peripheral B cell pool limited in self-reactive B cells that may produce pathogenic autoantibodies. To identify molecules regulating peripheral B cell survival and tolerance to self-antigens (Ags), a gene modifier screen was performed with B cells from CD22-deficient C57BL/6 (CD22(-/-[B6])) mice that undergo activation-induced cell death (AICD) and fail to up-regulate c-Myc expression after B cell Ag receptor ligation. Likewise, lysozyme auto-Ag-specific B cells in Ig(Tg) hen egg lysozyme (HEL) transgenic mice inhabit the spleen but undergo AICD after auto-Ag encounter. This gene modifier screen identified EndoU, a single-stranded RNA-binding protein of ancient origin, as a major regulator of B cell survival in both models. EndoU gene disruption prevents AICD and normalizes c-Myc expression. These findings reveal that EndoU is a critical regulator of an unexpected and novel RNA-dependent pathway controlling peripheral B cell survival and Ag responsiveness that may contribute to peripheral B cell tolerance. |
