title: Defective IgG2a/2b class switching in PKC alpha-/- mice.
abstract: Using model tumor T cell lines, protein kinase C (PKC) alpha has been implicated in IL-2 cytokine promoter activation in response to Ag receptor stimulation. In this study, for the first time, PKCalpha null mutant mice are analyzed and display normal T and B lymphocyte development. Peripheral CD3(+) PKCalpha-deficient T cells show unimpaired activation-induced IL-2 cytokine secretion, surface expression of CD25, CD44, and CD69, as well as transactivation of the critical transcription factors NF-AT, NF-kappaB, AP-1, and STAT5 in vitro. Nevertheless, CD3/CD28 Ab- and MHC alloantigen-induced T cell proliferation and IFN-gamma production are severely impaired in PKCalpha(-/-) CD3(+) T cells. Consistently, PKCalpha-deficient CD3(+) T cells from OVA-immunized PKCalpha-deficient mice exhibit markedly reduced recall proliferation to OVA in in vitro cultures. In vivo, PKCalpha-deficient mice give diminished OVA-specific IgG2a and IgG2b responses following OVA immunization experiments. In contrast, OVA-specific IgM and IgG1 responses and splenic PKCalpha(-/-) B cell proliferation are unimpaired. Our genetic data, thus, define PKCalpha as the physiological and nonredundant PKC isotype in signaling pathways that are necessary for T cell-dependent IFN-gamma production and IgG2a/2b Ab responses.
authors: Department for Medical Genetics, Molecular and Clinical Pharmacology, Medical University, Schoepfstrasse 41, A-6020 Innsbruck, Austria.
authors: Christa
authors: C
authors: Pfeifhofer
authors: Thomas
authors: T
authors: Gruber
authors: Thomas
authors: T
authors: Letschka
authors: Nikolaus
authors: N
authors: Thuille
authors: Christina
authors: C
authors: Lutz-Nicoladoni
authors: Natascha
authors: N
authors: Hermann-Kleiter
authors: Uschi
authors: U
authors: Braun
authors: Michael
authors: M
authors: Leitges
authors: Gottfried
authors: G
authors: Baier