Cutting edge: B cell–intrinsic T-bet expression is required to control chronic viral infection

BE Barnett, RP Staupe, PM Odorizzi… - The Journal of …, 2016 - journals.aai.org
BE Barnett, RP Staupe, PM Odorizzi, O Palko, VT Tomov, AE Mahan, B Gunn, D Chen…
The Journal of Immunology, 2016journals.aai.org
The role of Ab and B cells in preventing infection is established. In contrast, the role of B cell
responses in containing chronic infections remains poorly understood. IgG2a (IgG1 in
humans) can prevent acute infections, and T-bet promotes IgG2a isotype switching.
However, whether IgG2a and B cell–expressed T-bet influence the host–pathogen balance
during persisting infections is unclear. We demonstrate that B cell–specific loss of T-bet
prevents control of persisting viral infection. T-bet in B cells controlled IgG2a production, as …
Abstract
The role of Ab and B cells in preventing infection is established. In contrast, the role of B cell responses in containing chronic infections remains poorly understood. IgG2a (IgG1 in humans) can prevent acute infections, and T-bet promotes IgG2a isotype switching. However, whether IgG2a and B cell–expressed T-bet influence the host–pathogen balance during persisting infections is unclear. We demonstrate that B cell–specific loss of T-bet prevents control of persisting viral infection. T-bet in B cells controlled IgG2a production, as well as mucosal localization, proliferation, glycosylation, and a broad transcriptional program. T-bet controlled a broad antiviral program in addition to IgG2a because T-bet in B cells was important, even in the presence of virus-specific IgG2a. Our data support a model in which T-bet is a universal controller of antiviral immunity across multiple immune lineages.
journals.aai.org