Protein kinase Cdelta controls self-antigen-induced B-cell tolerance

Nature. 2002 Apr 25;416(6883):860-5. doi: 10.1038/416860a.


Interaction of a B cell expressing self-specific B-cell antigen receptor (BCR) with an auto-antigen results in either clonal deletion or functional inactivation. 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 anergy. Here we demonstrate that deficiency in protein kinase Cdelta (PKC-delta) 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-delta in B-cell tolerance is further underscored by the appearance of autoreactive anti-DNA and anti-nuclear antibodies in the serum of PKC-delta-deficient mice. As deficiency of PKC-delta does not affect BCR-mediated B-cell activation in vitro and in vivo, our data suggest a selective and essential role of PKC-delta in tolerogenic, but not immunogenic, B-cell responses.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Antinuclear / blood
  • Antibodies, Antinuclear / immunology
  • Antigens, CD / metabolism
  • Autoantigens / immunology*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B7-2 Antigen
  • Calcium / metabolism
  • Calcium Signaling
  • Cell Differentiation
  • Clonal Anergy / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Gene Deletion
  • Immune Tolerance / immunology*
  • Isoenzymes / deficiency
  • Isoenzymes / genetics
  • Isoenzymes / immunology
  • Isoenzymes / metabolism*
  • JNK Mitogen-Activated Protein Kinases
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Lymphocyte Activation
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitogen-Activated Protein Kinases / metabolism
  • Protein Kinase C / deficiency
  • Protein Kinase C / genetics
  • Protein Kinase C / immunology
  • Protein Kinase C / metabolism*
  • Protein Kinase C-delta
  • Signal Transduction
  • Spleen / cytology
  • Spleen / immunology


  • Antibodies, Antinuclear
  • Antigens, CD
  • Autoantigens
  • B7-2 Antigen
  • Cd86 protein, mouse
  • Isoenzymes
  • Membrane Glycoproteins
  • Prkcd protein, mouse
  • Protein Kinase C
  • Protein Kinase C-delta
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • Calcium