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

I Mecklenbräuker, K Saijo, NY Zheng, M Leitges… - Nature, 2002 - nature.com
I Mecklenbräuker, K Saijo, NY Zheng, M Leitges, A Tarakhovsky
Nature, 2002nature.com
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 …
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 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 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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