Memory B cells, but not long-lived plasma cells, possess antigen specificities for viral escape mutants.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Purtha, WE; Tedder, TF; Johnson, S; Bhattacharya, D; Diamond, MS

Published Date

  • December 19, 2011

Published In

Volume / Issue

  • 208 / 13

Start / End Page

  • 2599 - 2606

PubMed ID

  • 22162833

Pubmed Central ID

  • 22162833

Electronic International Standard Serial Number (EISSN)

  • 1540-9538

Digital Object Identifier (DOI)

  • 10.1084/jem.20110740

Language

  • eng

Conference Location

  • United States