Defective IgG2a/2b class switching in PKCα−/− mice

C Pfeifhofer, T Gruber, T Letschka, N Thuille… - The Journal of …, 2006 - journals.aai.org
C Pfeifhofer, T Gruber, T Letschka, N Thuille, C Lutz-Nicoladoni, N Hermann-Kleiter
The Journal of Immunology, 2006journals.aai.org
Using model tumor T cell lines, protein kinase C (PKC) α has been implicated in IL-2
cytokine promoter activation in response to Ag receptor stimulation. In this study, for the first
time, PKCα null mutant mice are analyzed and display normal T and B lymphocyte
development. Peripheral CD3+ PKCα-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-κB, AP-1, and STAT5 in vitro …
Abstract
Using model tumor T cell lines, protein kinase C (PKC) α has been implicated in IL-2 cytokine promoter activation in response to Ag receptor stimulation. In this study, for the first time, PKCα null mutant mice are analyzed and display normal T and B lymphocyte development. Peripheral CD3+ PKCα-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-κB, AP-1, and STAT5 in vitro. Nevertheless, CD3/CD28 Ab-and MHC alloantigen-induced T cell proliferation and IFN-γ production are severely impaired in PKCα−/− CD3+ T cells. Consistently, PKCα-deficient CD3+ T cells from OVA-immunized PKCα-deficient mice exhibit markedly reduced recall proliferation to OVA in in vitro cultures. In vivo, PKCα-deficient mice give diminished OVA-specific IgG2a and IgG2b responses following OVA immunization experiments. In contrast, OVA-specific IgM and IgG1 responses and splenic PKCα−/− B cell proliferation are unimpaired. Our genetic data, thus, define PKCα as the physiological and nonredundant PKC isotype in signaling pathways that are necessary for T cell-dependent IFN-γ production and IgG2a/2b Ab responses.
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