Plasmodium-specific atypical memory B cells are short-lived activated B cells

Elife. 2018 Nov 2:7:e39800. doi: 10.7554/eLife.39800.

Abstract

A subset of atypical memory B cells accumulates in malaria and several infections, autoimmune disorders and aging in both humans and mice. It has been suggested these cells are exhausted long-lived memory B cells, and their accumulation may contribute to poor acquisition of long-lasting immunity to certain chronic infections, such as malaria and HIV. Here, we generated an immunoglobulin heavy chain knock-in mouse with a BCR that recognizes MSP1 of the rodent malaria parasite, Plasmodium chabaudi. In combination with a mosquito-initiated P. chabaudi infection, we show that Plasmodium-specific atypical memory B cells are short-lived and disappear upon natural resolution of chronic infection. These cells show features of activation, proliferation, DNA replication, and plasmablasts. Our data demonstrate that Plasmodium-specific atypical memory B cells are not a subset of long-lived memory B cells, but rather short-lived activated cells, and part of a physiologic ongoing B-cell response.

Keywords: FCRL5; Plasmodium; age-associated B cells; atypical memory B cells; immunology; infectious disease; inflammation; malaria; microbiology; mosquito; mouse.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocyte Subsets / chemistry
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocytes / chemistry
  • B-Lymphocytes / immunology*
  • Flow Cytometry
  • Gene Knock-In Techniques
  • Immunoglobulin G / genetics
  • Immunologic Memory*
  • Malaria / immunology
  • Merozoite Surface Protein 1 / immunology*
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Plasmodium chabaudi / immunology*
  • Rodent Diseases / immunology

Substances

  • Immunoglobulin G
  • Merozoite Surface Protein 1