International Immunology, Vol. 15, No. 8, pp. 937-944,
August 2003
© 2003 Japanese Society for Immunology
T-bet regulates T-independent IgG2a class switching
Departments of 1 Internal Medicine and 2 Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA
Correspondence to: S. L. Peng, Department of Internal Medicine/Rheumatology, Campus Box 8045, CSRB 6617, 660 South Euclid Avenue, St Louis, MO 63110, USA. E-mail: speng{at}im.wustl.edu
Transmitting editor: K. M. Murphy
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.
Keywords: antibody, B lymphocyte, cellular activation, rodent
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