Protein phosphatase subunit G5PR is needed for inhibition of B cell receptor–induced apoptosis

B cell receptor (BCR) cross-linking induces B cell proliferation and sustains survival through the phosphorylation-dependent signals. We report that a loss of the protein phosphatase component G5PR increased the activation-induced cell death (AICD) and thus impaired B cell survival. G5PR associates with GANP, whose expression is up-regulated in mature B cells of the peripheral lymphoid organs. To study G5PR function, the G5pr gene was conditionally targeted with the CD19-Cre combination (G5pr−/− mice). The G5pr−/− mice had a decreased number of splenic B cells (60% of the controls). G5pr−/− B cells showed a normal proliferative response to lipopolysaccharide or anti-CD40 antibody stimulation but not to BCR cross-linking with or without IL-4 in vitro. G5pr−/− B cells did not show abnormalities in the BCR-mediated activation of Erks and NF-κB, cyclin D2 induction, or Akt activation. However, G5pr−/− B cells were sensitive to AICD caused by BCR cross-linking. This was associated with an increased depolarization of the mitochondrial membrane and the enhanced activation of c-Jun NH2-terminal protein kinase and Bim. These results suggest that G5PR is required for the BCR-mediated proliferation associated with the prevention of AICD in mature B cells

LL55: Selective Early Lymphoid Expression of a Murine cDNA Clone Which Encodes a Putative RNA-Binding Protein

Specific expression of various RNA-binding protein (RNP) molecules is one of the critical factors that determine the development in Drosophila melanogaster and Caenorhabditis elegans. In the present study, we found a complementary DNA clone, LL55 encoding a putative RNP. Structural comparison of nucleotide and amino acid sequences demonstrate that LL55 encoding a nuclear protein with two RNA-binding consensus motifs and the common arginine-serine repeats, is similar to the sex-determining transformer-2 (tra-2) gene of Drosophila melanogaster. The expression of 2.3 kilobase (kb) and 1.5 kb LL55 messenger RNA (mRNA) is ubiquitous in murine organs and tissues, but it is selective in the early development of fetal life. It appears as early as day 10.5 and increases until day 15 of gestation in accordance with the expression of λ5 mRNA which is involved in murine pre-B cell generation. Taking account of the selective expression and the specific regulation of RNP molecules, the finding of LL55 RNP provides a new outlook for the generation and function of the immune system