Publications & Reports

FCRL5 Delineates Functionally Impaired Memory B Cells Associated with Plasmodium falciparum Exposure.

Sullivan RT, Kim CC, Fontana MF, Feeney ME, Jagannathan P, Boyle MJ, Drakeley CJ, Ssewanyana I, Nankya F, Mayanja-Kizza H, Dorsey G, Greenhouse B
Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, San Francisco, California, United States of America.

Abstract

Exposure to Plasmodium falciparum is associated with circulating “atypical” memory B cells (atMBCs), which appear similar to dysfunctional B cells found in HIV-infected individuals. Functional analysis of atMBCs has been limited, with one report suggesting these cells are not dysfunctional but produce protective antibodies. To better understand the function of malaria-associated atMBCs, we performed global transcriptome analysis of these cells, obtained from individuals living in an area of high malaria endemicity in Uganda. Comparison of gene expression data suggested down-modulation of B cell receptor signaling and apoptosis in atMBCs compared to classical MBCs. Additionally, in contrast to previous reports, we found upregulation of Fc receptor-like 5 (FCRL5), but not FCRL4, on atMBCs. Atypical MBCs were poor spontaneous producers of antibody ex vivo, and higher surface expression of FCRL5 defined a distinct subset of atMBCs compromised in its ability to produce antibody upon stimulation. Moreover, higher levels of P. falciparum exposure were associated with increased frequencies of FCRL5+ atMBCs. Together, our findings suggest that FCLR5+ identifies a functionally distinct, and perhaps dysfunctional, subset of MBCs in individuals exposed to P. falciparum.

Publication

  • Journal: PLoS Pathogens
  • Published: 01/05/2015
  • Volume: 11
  • Issue: 5
  • Pagination: e1004894

Health Issue

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