| First Author | Gerth AJ | Year | 2003 |
| Journal | Int Immunol | Volume | 15 |
| Issue | 8 | Pages | 937-44 |
| PubMed ID | 12882831 | Mgi Jnum | J:84929 |
| Mgi Id | MGI:2670820 | Doi | 10.1093/intimm/dxg093 |
| Citation | Gerth AJ, et al. (2003) T-bet regulates T-independent IgG2a class switching. Int Immunol 15(8):937-44 |
| abstractText | The IgG2a Ig subclass plays a critical role in the pathogenesis of humoral autoimmunity and protection against pathogens. The T-box transcription factor T-bet has been implicated as a critical mediator of class-switch recombination (CSR) to IgG2a, but its relative importance to this process in various immune contexts remains incompletely defined. We report here that, surprisingly, T-bet is selectively required for IgG2a class switching in response to T-independent, but not T-dependent, stimuli. Specifically, T-dependent signaling through CD40, in contrast to T-independent signaling via lipopolysaccharide, can bypass a requirement for T-bet in IgG2a germline transcription and subsequent isotype switching. In contrast, T-bet-deficient B cells undergo class switching to other IgG isotypes at least as well as wild-type counterparts. Thus, T-bet is a class-specific regulator of IgG CSR and represents a unique regulator of B cell differentiation by participating in a T-independent, but not a T-dependent, activation pathway. T-bet-deficient B cells therefore represent a novel paradigm by which to investigate the regulation of humoral immune responses. |
