ArticleMolecular and cellular biology2014
Protein kinase Cδ promotes transitional B cell-negative selection and limits proximal B cell receptor signaling to enforce tolerance.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Expanding the scope of PI3K-δ inhibition: Leniolisib treatment in PRKCD deficiency.Journal of human immunity · 2026Article
- Dynamic feedback control of oncogenic tyrosine kinase signaling in acute leukemia.Science signaling · 2026Article
- Restoring B cell intrinsic tolerance to lupus autoimmunity: a rational strategy for lupus treatment.Frontiers in immunology · 2026Review
- PKCδ Protects against Lupus Autoimmunity.Biomedicines · 2024Review
- Phenotypic Variability in PRKCD: a Review of the Literature.Journal of clinical immunology · 2023Review
- Genes and Microbiota Interaction in Monogenic Autoimmune Disorders.Biomedicines · 2023Review
- Impaired respiratory burst contributes to infections in PKCδ-deficient patients.The Journal of experimental medicine · 2021Article
- Quantitative phosphoproteomic analysis reveals involvement of PD-1 in multiple T cell functions.The Journal of biological chemistry · 2020Article
- Monogenic systemic lupus erythematosus: insights in pathophysiology.Rheumatology international · 2018Review
- Autoimmunity checkpoints as therapeutic targets in B cell malignancies.Nature reviews. Cancer · 2018Review
- CD5 expression promotes IL-10 production through activation of the MAPK/Erk pathway and upregulation of TRPC1 channels in B lymphocytes.Cellular & molecular immunology · 2018Article
- Effective Combination Therapies for B-cell Lymphoma Predicted by a Virtual Disease Model.Cancer research · 2017Article
- Protein Kinase C δ: a Gatekeeper of Immune Homeostasis.Journal of clinical immunology · 2016Review
- Activation of Ras overcomes B-cell tolerance to promote differentiation of autoreactive B cells and production of autoantibodies.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
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Authors and funding
6 authors.
Funding
Abstract
Protein kinase Cδ (PKCδ) 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 PKCδ deficiency remain poorly defined. Here, we address 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-activating factor (BAFF) receptor. We found that PKCδ 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 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.
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