コンテンツへスキップ
Merck
  • The intramembrane protease Sppl2a is required for B cell and DC development and survival via cleavage of the invariant chain.

The intramembrane protease Sppl2a is required for B cell and DC development and survival via cleavage of the invariant chain.

The Journal of experimental medicine (2012-12-26)
Daniel R Beisner, Petra Langerak, Albert E Parker, Carol Dahlberg, Francella J Otero, Sue E Sutton, Laurent Poirot, Whitney Barnes, Michael A Young, Sherry Niessen, Tim Wiltshire, Ursula Bodendorf, Bruno Martoglio, Benjamin Cravatt, Michael P Cooke
要旨

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.

材料
製品番号
ブランド
製品内容

Sigma-Aldrich
N-ニトロソ-N-エチル尿素, ISOPAC®
Sigma-Aldrich
N-ニトロソ-N-エチル尿素, Bulk package