Increased proliferation of B cells and auto-immunity in mice lacking protein kinase Cδ

Akitomo Miyamoto, Keiko Nakayama, Hiroyuki Imaki, Sachiko Hirose, Yi Jiang, Masaaki Abe, Tadasuke Tsukiyama, Hiroyasu Nagahama, Shigeo Ohno, Shigetsugu Hatakeyama and Keiichi I. Nakayama ()
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Akitomo Miyamoto: Medical Institute of Bioregulation, Kyushu University
Keiko Nakayama: CREST, Japan Science and Technology Corporation
Hiroyuki Imaki: Medical Institute of Bioregulation, Kyushu University
Sachiko Hirose: CREST, Japan Science and Technology Corporation
Yi Jiang: Juntendo University School of Medicine
Masaaki Abe: Juntendo University School of Medicine
Tadasuke Tsukiyama: Medical Institute of Bioregulation, Kyushu University
Hiroyasu Nagahama: Medical Institute of Bioregulation, Kyushu University
Shigeo Ohno: Yokohama City University School of Medicine
Shigetsugu Hatakeyama: Medical Institute of Bioregulation, Kyushu University
Keiichi I. Nakayama: Medical Institute of Bioregulation, Kyushu University

Nature, 2002, vol. 416, issue 6883, 865-869

Abstract: 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 development1,2,3,4. Among the PKC isotypes, PKC-δ is unique in that its overexpression results in inhibition of cell growth5,6,7,8,9,10,11. Here we show that mice that lack PKC-δ 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-δ-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-δ-null mice as a result of an increase in the DNA-binding activity of NF-IL6. Furthermore, the PKC-δ-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-δ has an indispensable function in negative regulation of B-cell proliferation, and is particularly important for the establishment of B-cell tolerance.

Date: 2002
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DOI: 10.1038/416865a

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