Abstract
Interaction of a B cell expressing self-specific B-cell antigen receptor (BCR) with an auto-antigen results in either clonal deletion or functional inactivation1,2,3. Both of these processes lead to B-cell tolerance and are essential for the prevention of auto-immune diseases. Whereas clonal deletion results in the death of developing autoreactive B cells, functional inactivation of self-reactive B lymphocytes leads to complex changes in the phenotype of peripheral B cells, described collectively as anergy1,2,3. Here we demonstrate that deficiency in protein kinase Cδ (PKC-δ) prevents B-cell tolerance, and allows maturation and terminal differentiation of self-reactive B cells in the presence of the tolerizing antigen. The importance of PKC-δ in B-cell tolerance is further underscored by the appearance of autoreactive anti-DNA and anti-nuclear antibodies in the serum of PKC-δ-deficient mice. As deficiency of PKC-δ does not affect BCR-mediated B-cell activation in vitro and in vivo, our data suggest a selective and essential role of PKC-δ in tolerogenic, but not immunogenic, B-cell responses.
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Acknowledgements
We thank C. Goodnow, J. Cyster and F. Finkelman for providing reagents; members of the Laboratory for Lymphocyte Signaling in Cologne for technical assistance; and G. Hannon for the preparation of the manuscript. We thank M. Nussenzweig, D. O′Carrol, K. Rajewsky and C. Schmedt for discussion. This work was supported by The Irene Diamond Fund (A.T.) and National Institutes of Health grant (N-Y.Z. and A.T.), S. L. E. Foundation (K.S.), Graduiertenkolleg from the Deutsche Forschungsgemeinschaft, and The Rockefeller University's Women & Science Fellowship Program (I.M.).
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Mecklenbräuker, I., Saijo, K., Zheng, NY. et al. Protein kinase Cδ controls self-antigen-induced B-cell tolerance. Nature 416, 860–865 (2002). https://doi.org/10.1038/416860a
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DOI: https://doi.org/10.1038/416860a
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