Defective IgG2a/2b class switching in PKC alpha-/- mice

J Immunol. 2006 May 15;176(10):6004-11. doi: 10.4049/jimmunol.176.10.6004.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD3 Complex / biosynthesis
  • Cell Proliferation
  • Cells, Cultured
  • Immunoglobulin Class Switching / genetics*
  • Immunoglobulin G / classification*
  • Immunoglobulin G / genetics*
  • Immunoglobulin Isotypes / genetics*
  • Interferon-gamma / biosynthesis
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Kinase C-alpha / deficiency*
  • Protein Kinase C-alpha / genetics*
  • Protein Kinase C-alpha / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism


  • CD3 Complex
  • Immunoglobulin G
  • Immunoglobulin Isotypes
  • Interferon-gamma
  • Protein Kinase C-alpha