Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 34, Pages E3216-E3224Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1312348110
Keywords
interferon gamma; virus
Categories
Funding
- US Public Health Service [AI-18785, AI-22295]
- T32 training grant award [AI074491]
- NATIONAL CANCER INSTITUTE [R01CA168558, R01CA103632] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI018785, R37AI018785, R56AI018785, T32AI074491, P01AI022295] Funding Source: NIH RePORTER
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IgG2a is known to be the most efficient antibody isotype for viral clearance. Here, we demonstrate a unique pathway of B-cell activation, leading to IgG2a production, and involving synergistic stimulation via B-cell antigen receptors, toll-like receptor 7 (TLR7), and IFN gamma receptors on B cells. This synergistic stimulation leads to induction of T-box transcription factor T-bet expression in B cells, which, in turn, drives expression of CD11b and CD11c on B cells. T-bet/CD11b/CD11c positive B cells appear during antiviral responses and produce high titers of antiviral IgG2a antibodies that are critical for efficient viral clearance. The results thus demonstrate a previously unknown role for T-bet expression in B cells during viral infections. Moreover, the appearance of T-bet(+) B cells during antiviral responses and during autoimmunity suggests a possible link between these two processes.
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