1. Laboratory of Lymphocyte Signaling, The Rockefeller University, New York, New York 10021, USA
2. Max Planck Institute for Experimental Endocrinology, D-30625 Hannover, Germany

Correspondence to: Alexander Tarakhovsky¹ Correspondence and requests for materials should be addressed to A.T. (e-mail: Email: tarakho@mail.rockefeller.edu).

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^{1, 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 anergy^{1, 2, 3}. Here we demonstrate that deficiency in protein kinase C (PKC-) 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- in B-cell tolerance is further underscored by the appearance of autoreactive anti-DNA and anti-nuclear antibodies in the serum of PKC--deficient mice. As deficiency of PKC- does not affect BCR-mediated B-cell activation in vitro and in vivo, our data suggest a selective and essential role of PKC- in tolerogenic, but not immunogenic, B-cell responses.