| First Author | Beisner DR | Year | 2013 |
| Journal | J Exp Med | Volume | 210 |
| Issue | 1 | Pages | 23-30 |
| PubMed ID | 23267013 | Mgi Jnum | J:194595 |
| Mgi Id | MGI:5474389 | Doi | 10.1084/jem.20121072 |
| Citation | Beisner DR, et al. (2013) The intramembrane protease Sppl2a is required for B cell and DC development and survival via cleavage of the invariant chain. J Exp Med 210(1):23-30 |
| abstractText | B cell development requires tight regulation to allow for the generation of a diverse repertoire while preventing the development of autoreactive cells. We report, using N-ethyl-N-nitrosourea (ENU)-induced mutagenesis, the identification of a mutant mouse (chompB) with a block in early B cell development. The blockade occurs after the transitional 1 (T1) stage and leads to a decrease in mature B cell subsets and deficits in T cell-dependent antibody responses. Additionally, chompB mice have decreases in myeloid dendritic cells (DCs). The mutation was mapped to the intramembrane protease signal peptide peptidase-like 2a (Sppl2a), a gene not previously implicated in immune cell development. Proteomic analysis identified the invariant chain (CD74) as a key substrate of Sppl2a and suggests that regulated intramembrane proteolysis of CD74 by Sppl2a contributes to B cell and DC survival. Moreover, these data suggest that modulation of Sppl2a may be a useful therapeutic strategy for treatment of B cell dependent autoimmune disorders. |
