| First Author | Gao Y | Year | 2012 |
| Journal | Int Immunol | Volume | 24 |
| Issue | 5 | Pages | 283-92 |
| PubMed ID | 22301689 | Mgi Jnum | J:184089 |
| Mgi Id | MGI:5320243 | Doi | 10.1093/intimm/dxr127 |
| Citation | Gao Y, et al. (2012) Bim regulates B-cell receptor-mediated apoptosis in the presence of CD40 signaling in CD40-pre-activated splenic B cells differentiating into plasma cells. Int Immunol 24(5):283-92 |
| abstractText | B-cell receptor (BCR)-mediated apoptosis is critical for B-cell development and homeostasis. CD40 signaling has been shown to protect immature or mature B cells from BCR-mediated apoptosis. In this study, to understand the fate of CD40-pre-activated splenic B cells stimulated by BCR engagement in the presence of CD40 signaling, murine splenic B cells were cultured with anti-Igkappa and anti-CD40 antibodies after pre-activation with anti-CD40 antibody. We found that apoptosis was induced in the cultured B cells even in the presence of CD40 signaling during the 3-4 days cultivation. We detected up-regulation of Bim expression followed by Bax activation in this apoptotic process and cessation of the apoptosis in Bim-deficient B cells, indicating that Bim is a key regulator of the BCR-mediated apoptosis in the presence of CD40 signaling in CD40-pre-activated B cells. Importantly, this BCR-mediated apoptosis in CD40-pre-activated B cells was shown to be induced at the initiation of plasma cell differentiation at around the preplasmablast stage, and Bim-deficient B cells cultured under these conditions differentiated into plasma cells. Additionally, transforming growth factor-beta was found to protect CD40-pre-activated B cells from BCR-mediated apoptosis in the presence of CD40 signaling. Our identified BCR-mediated apoptosis, which is unpreventable by CD40 signaling, suggests a potential mechanism that regulates the elimination of peripheral B cells, which should be derived from nonspecific T-dependent activation of bystander B cells and continuous stimulation with antigens including self-antigens in the presence of T cell help through CD40. |
