| First Author | Hanihara-Tatsuzawa F | Year | 2014 |
| Journal | J Biol Chem | Volume | 289 |
| Issue | 45 | Pages | 30925-36 |
| PubMed ID | 25124037 | Mgi Jnum | J:217074 |
| Mgi Id | MGI:5613038 | Doi | 10.1074/jbc.M114.553230 |
| Citation | Hanihara-Tatsuzawa F, et al. (2014) Control of Toll-like receptor-mediated T cell-independent type 1 antibody responses by the inducible nuclear protein IkappaB-zeta. J Biol Chem 289(45):30925-36 |
| abstractText | 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 IkappaB-zeta, specifically in their B cells, have impaired TI-1 antibody responses but normal T cell-dependent and TI-2 antibody responses. The absence of IkappaB-zeta in B cells also impaired proliferation triggered by Toll-like receptor (TLR) activation, plasma cell differentiation, and class switch recombination (CSR). Mechanistically, IkappaB-zeta-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 IkappaB-zeta-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 IkappaB-zeta-deficient B cells relative to IkappaB-zeta-expressing B cells. These results indicate that IkappaB-zeta regulates TLR-mediated CSR by inducing AID. Moreover, IkappaB-zeta defines differences in the transcriptional regulation of different antibody responses. |
