| First Author | Limnander A | Year | 2014 |
| Journal | Mol Cell Biol | Volume | 34 |
| Issue | 8 | Pages | 1474-85 |
| PubMed ID | 24515435 | Mgi Jnum | J:213625 |
| Mgi Id | MGI:5585396 | Doi | 10.1128/MCB.01699-13 |
| Citation | Limnander A, et al. (2014) Protein kinase Cdelta promotes transitional B cell-negative selection and limits proximal B cell receptor signaling to enforce tolerance. Mol Cell Biol 34(8):1474-85 |
| abstractText | Protein kinase Cdelta (PKCdelta) deficiency causes autoimmune pathology in humans and mice and is crucial for the maintenance of B cell homeostasis. However, the mechanisms underlying autoimmune disease in PKCdelta deficiency remain poorly defined. Here, we address the antigen-dependent and -independent roles of PKCdelta in B cell development, repertoire selection, and antigen responsiveness. We demonstrate that PKCdelta is rapidly phosphorylated downstream of both the B cell receptor (BCR) and the B cell-activating factor (BAFF) receptor. We found that PKCdelta is essential for antigen-dependent negative selection of splenic transitional B cells and is required for activation of the proapoptotic Ca(2+)-Erk pathway that is selectively activated during B cell-negative selection. Unexpectedly, we also identified a previously unrecognized role for PKCdelta as a proximal negative regulator of BCR signaling that substantially impacts survival and proliferation of mature follicular B cells. As a consequence of these distinct roles, PKCdelta deficiency leads to the survival and development of a B cell repertoire that is not only aberrantly autoreactive but also hyperresponsive to antigen stimulation. |
