PMID:11976687

Citation	Miyamoto, A, Nakayama, K, Imaki, H, Hirose, S, Jiang, Y, Abe, M, Tsukiyama, T, Nagahama, H, Ohno, S, Hatakeyama, S and Nakayama, KI (2002) Increased proliferation of B cells and auto-immunity in mice lacking protein kinase Cdelta. Nature 416:865-9
Abstract	Protein kinase C (PKC), which comprises 11 closely related isoforms, has been implicated in a wide variety of cellular processes, such as growth, differentiation, secretion, apoptosis and tumour development. Among the PKC isotypes, PKC-delta is unique in that its overexpression results in inhibition of cell growth. Here we show that mice that lack PKC-delta exhibit expansion of the B-lymphocyte population with the formation of numerous germinal centres in the absence of stimulation. The rate of proliferation in response to stimulation was greater for B cells from PKC-delta-deficient mice than for those from wild-type mice. Adoptive transfer experiments suggested that the hyperproliferation phenotype is B-cell autonomous. Production of interleukin-6 was markedly increased in B cells of PKC-delta-null mice as a result of an increase in the DNA-binding activity of NF-IL6. Furthermore, the PKC-delta-deficient mice contain circulating autoreactive antibodies and display immune-complex-type glomerulonephritis, as well as lymphocyte infiltration in many organs. These results suggest that PKC-delta has an indispensable function in negative regulation of B-cell proliferation, and is particularly important for the establishment of B-cell tolerance.
Links	PubMed Online version:10.1038/416865a
Keywords	Adoptive Transfer; Animals; Autoantibodies/blood; Autoimmunity/immunology; B-Lymphocytes/cytology; B-Lymphocytes/immunology; B-Lymphocytes/transplantation; CCAAT-Enhancer-Binding Protein-beta/metabolism; Cell Division; Flow Cytometry; Gene Deletion; Genes, RAG-1/genetics; Glomerulonephritis/immunology; Glomerulonephritis/pathology; Immune Tolerance/immunology; Immunoglobulin A/blood; Immunoglobulin G/blood; Interleukin-10/genetics; Interleukin-6/biosynthesis; Interleukin-6/genetics; Isoenzymes/deficiency; Isoenzymes/genetics; Isoenzymes/metabolism; Kidney/immunology; Kidney/pathology; Lymph Nodes/cytology; Lymph Nodes/immunology; Mice; Mice, Knockout; Protein Kinase C/deficiency; Protein Kinase C/genetics; Protein Kinase C/metabolism; Protein Kinase C-delta; Spleen/cytology; Spleen/immunology; T-Lymphocytes/cytology; T-Lymphocytes/immunology
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