Protein kinase Cδ promotes transitional B cell-negative selection and limits proximal B cell receptor signaling to enforce tolerance
| Autor: | Michael Leitges, Jeroen P. Roose, Andre Limnander, Tannia Lau, Julie Zikherman, Arthur Weiss |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Precursor Cells
Knockout 1.1 Normal biological development and functioning B-cell receptor Receptors Antigen B-Cell Biology Inbred C57BL Lymphocyte Activation Autoimmune Disease Medical and Health Sciences Mice B cell homeostasis Underpinning research Receptors B-Cell Activating Factor medicine Immune Tolerance Animals 2.1 Biological and endogenous factors Phosphorylation Aetiology B cell negative selection B-cell activating factor Protein kinase A Receptor Molecular Biology B cell B-Lymphoid Mice Knockout B-Lymphocytes Precursor Cells B-Lymphoid Inflammatory and immune system breakpoint cluster region B-Cell Cell Differentiation Articles Cell Biology Biological Sciences Cell biology Mice Inbred C57BL Protein Kinase C-delta medicine.anatomical_structure Antigen Signal Transduction Developmental Biology |
| Zdroj: | Limnander, A; Zikherman, J; Lau, T; Leitges, M; Weiss, A; & Roose, JP. (2014). Protein kinase Cδ promotes transitional B cell-negative selection and limits proximal B cell receptor signaling to enforce tolerance. Molecular and Cellular Biology, 34(8), 1474-1485. doi: 10.1128/MCB.01699-13. UCSF: Retrieved from: http://www.escholarship.org/uc/item/3jj9q4g2 Molecular and cellular biology, vol 34, iss 8 |
| Popis: | Protein kinase Cδ (PKCδ) deficiency causes autoimmune pathology in humansand mice and is crucial for the maintenance of B cell homeostasis. However, the mechanisms underlying autoimmune disease in PKCδ deficiency remain poorly defined. Here, weaddress the antigen-dependent and -independent roles of PKCδ in B cell development, repertoire selection, and antigen responsiveness. We demonstrate that PKCδ is rapidly phosphorylated downstream of both the B cell receptor (BCR) and the B cell-activatingfactor (BAFF) receptor. Wefound that PKCδ is essential for antigen-dependent negative selection of splenic transitional B cells and is required for activation of the proapoptotic Ca2+-Erk pathway that is selectively activated during B cell-negative selection. Unexpectedly, we also identified a previously unrecognized role for PKCδ 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, PKCδ deficiency leads to the survival and development of a B cell repertoire that is not only aberrantly autoreactive but also hyperresponsive to antigen stimulation. © 2014, American Society for Microbiology. |
| Databáze: | OpenAIRE |
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