T-Bet Enables Tissue-Restricted B Cell Memory and Influenza Hemagglutinin Stalk-Specific Antibodies
48 Pages Posted: 25 Oct 2018 Sneak Peek Status: PublishedMore...
We describe two functionally distinct influenza hemagglutinin (HA)-specific memory B cell populations (Bmem) in mice and humans, distinguished by T-bet expression. In mice, both T-bet- and T-bet HA-specific B cells emerge within 6 days of influenza infection, persist indefinitely, and transiently express the memory markers CD38, CD73, PD-L2 and CD80. However, while T-bet- Bmem arise in all secondary lymphoid tissues and recirculate, T-bet Bmem neither arise nor migrate within lymphatics, but remain in the spleen. Human HA-specific Bmem display similar features: while T-bet- Bmem are found in all secondary lymphoid tissues, T-bet Bmem are exclusively found in spleen and blood. Using conditional T-bet knockout mice, we show that T-bet B cells are required for the majority of neutralizing and HA stalk-specific IgG2a/c antibodies. Together, these findings show T-bet expression is a durable and conserved feature that discriminates Bmem with distinct origins, tissue distributions, and epitope specificities.
Keywords: Humoral immunity, B cell memory, influenza, T-bet B cells
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