RRC ID 45235
Author Hanihara-Tatsuzawa F, Miura H, Kobayashi S, Isagawa T, Okuma A, Manabe I, MaruYama T.
Title Control of Toll-like receptor-mediated T cell-independent type 1 antibody responses by the inducible nuclear protein IκB-ζ.
Journal J. Biol. Chem.
Abstract Antibody responses have been classified as being either T cell-dependent or T cell-independent (TI). TI antibody responses are further classified as being either type 1 (TI-1) or type 2 (TI-2), depending on their requirement for B cell-mediated antigen receptor signaling. Although the mechanistic basis of antibody responses has been studied extensively, it remains unclear whether different antibody responses share similarities in their transcriptional regulation. Here, we show that mice deficient in IκB-ζ, specifically in their B cells, have impaired TI-1 antibody responses but normal T cell-dependent and TI-2 antibody responses. The absence of IκB-ζ in B cells also impaired proliferation triggered by Toll-like receptor (TLR) activation, plasma cell differentiation, and class switch recombination (CSR). Mechanistically, IκB-ζ-deficient B cells could not induce TLR-mediated induction of activation-induced cytidine deaminase (AID), a class-switch DNA recombinase. Retroviral transduction of AID in IκB-ζ-deficient B cells restored CSR activity. Furthermore, acetylation of histone H3 in the vicinity of the transcription start site of the gene that encodes AID was reduced in IκB-ζ-deficient B cells relative to IκB-ζ-expressing B cells. These results indicate that IκB-ζ regulates TLR-mediated CSR by inducing AID. Moreover, IκB-ζ defines differences in the transcriptional regulation of different antibody responses.
Volume 289(45)
Pages 30925-36
Published 2014-11-7
DOI 10.1074/jbc.M114.553230
PII M114.553230
PMID 25124037
PMC PMC4223300
MeSH Adaptor Proteins, Signal Transducing / metabolism* Alleles Animals Antibody Formation / immunology B-Lymphocytes / metabolism* CD40 Antigens / metabolism Cell Differentiation Cell Line Cell Proliferation Cytidine Deaminase / metabolism Gene Expression Regulation* Histones / chemistry Immunoglobulin Class Switching Lipopolysaccharides / chemistry Mice Nuclear Proteins / metabolism* Receptors, Antigen, B-Cell / metabolism Recombinases / metabolism Recombination, Genetic Signal Transduction Spleen / cytology T-Lymphocytes / immunology* Toll-Like Receptors / immunology Toll-Like Receptors / metabolism*
IF 4.011
Times Cited 7
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Human and Animal Cells