Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 208, Issue 13, Pages 2599-2606Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20110740
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Funding
- National Institutes of Health (Midwest and Southeastern Regional Centers of Excellence for Biodefense and Emerging Infectious Diseases Research) [U54 AI057160, U54 AI057157, R01 AI56363, U01 AI082196]
- Children's Discovery Institute [PD-II-2011-116]
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Memory B cells (MBCs) and long-lived plasma cells (LLPCs) persist after clearance of infection, yet the specific and nonredundant role MBCs play in subsequent protection is unclear. After resolution of West Nile virus infection in mice, we demonstrate that LLPCs were specific for a single dominant neutralizing epitope, such that immune serum poorly inhibited a variant virus that encoded a mutation at this critical epitope. In contrast, a large fraction of MBC produced antibody that recognized both wild-type (WT) and mutant viral epitopes. Accordingly, antibody produced by the polyclonal pool of MBC neutralized WT and variant viruses equivalently. Remarkably, we also identified MBC clones that recognized the mutant epitope better than the WT protein, despite never having been exposed to the variant virus. The ability of MBCs to respond to variant viruses in vivo was confirmed by experiments in which MBCs were adoptively transferred or depleted before secondary challenge. Our data demonstrate that class-switched MBC can respond to variants of the original pathogen that escape neutralization of antibody produced by LLPC without a requirement for accumulating additional somatic mutations.
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