International Immunology, Vol. 14, No. 9, pp. 983-991,
September 2002
© 2002 Japanese Society for Immunology
FEATURED ARTICLE OF THE MONTH |
Regulation of Ig class switch recombination by NF-
B: retroviral expression of RelB in activated B cells inhibits switching to IgG1, but not to IgE
1 Division of Immunology, Cancer Research Laboratory, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3200, USA
Correspondence to: W. C. Sha; E-mail: bsha{at}uclink4.berkeley.edu
Transmitting editor: K. Murphy
Mutant NF-
B-deficient B cells from knockout mice lacking RelA, p105/p50 or the transactivation domain of c-Rel exhibit distinct and selective cell-intrinsic defects in their ability to undergo class switch recombination (CSR) to specific Ig isotypes. This isotype-specific requirement for particular NF-B transcription factors in B cells activated to undergo CSR is intriguing because the NF-B composition in B cells is also highly regulated and can vary significantly depending upon how B cells are activated. These studies prompted us to test by retroviral transduction of normal B cells whether changes in the NF-B composition in activated B cells could modulate cytokine-driven CSR. RelB, RelA, c-Rel, p50 and p52 were first expressed in lipopolysaccharide-activated primary B cells and then induced by cytokine addition to undergo CSR to IgG1, IgE, IgG2a, IgG2b or IgA. Surprisingly, only retroviral expression of RelB altered CSR, resulting in a 3-fold decrease in CSR to IgG1 induced by IL-4. This effect was isotype specific as RelB expression did not affect CSR to IgE within the same culture or to other isotypes tested. The transactivation domain of RelB was required for inhibition of CSR to IgG1. Expression of p50–RelB or p52–RelB dimers joined covalently by a flexible peptide linker also specifically inhibited IgG1 CSR. RelB-mediated inhibition of IgG1 CSR was associated with a decrease in germline 
1 transcription, but not with changes in proliferation as assayed by CFSE labeling. Thus, RelB complexes can specifically inhibit CSR to IgG1, but not IgE, in activated, primary B cells.
Keywords: IL-4, isotype switching, lipopolysaccharide, retrovirus, splenic B cells
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