Abstract
The B cell-activating factor (BAFF) is critical for B cell development and humoral immunity in mice and humans. While the role of BAFF in B cells has been widely described, its role in innate immunity remains unknown. Using BAFF receptor (BAFFR)-deficient mice, we characterized BAFFR-related innate and adaptive immune functions following infection with vesicular stomatitis virus (VSV) and lymphocytic choriomeningitis virus (LCMV).Weidentified a critical role for BAFFR signaling in the generation and maintenance of the CD169+ macrophage compartment. Consequently, Baffr-/- mice exhibited limited induction of innate type I interferon production after viral infection. Lack of BAFFR signaling reduced virus amplification and presentation following viral infection, resulting in highly reduced antiviral adaptive immune responses. As a consequence, BAFFR-deficient mice showed exacerbated and fatal disease after viral infection. Mechanistically, transient lack of B cells in Baffr-/- animals resulted in limited lymphotoxin expression, which is critical for maintenance of CD169+ cells. In conclusion, BAFFR signaling affects both innate and adaptive immune activation during viral infections.
Original language | English |
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Pages (from-to) | 4748-4759 |
Number of pages | 12 |
Journal | Journal of Virology |
Volume | 89 |
Issue number | 9 |
DOIs | |
Publication status | Published - 2015 |
Externally published | Yes |