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

Whitney E. Purtha, Thomas F. Tedder, Syd Johnson, Deepta Bhattacharya, Michael S. Diamond

Research output: Contribution to journalArticlepeer-review

137 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2599-2606
Number of pages8
JournalJournal of Experimental Medicine
Volume208
Issue number13
DOIs
StatePublished - Dec 19 2011
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'Memory B cells, but not long-lived plasma cells, possess antigen specificities for viral escape mutants'. Together they form a unique fingerprint.

Cite this