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PLoS Pathog. 2015 May 19;11(5):e1004894. doi: 10.1371/journal.ppat.1004894. eCollection 2015 May.

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

Author information

1
Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, San Francisco, California, United States of America.
2
Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California, United States of America.
3
Division of HIV/AIDS, Department of Medicine, University of California, San Francisco, San Francisco, California, United States of America.
4
Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California, United States of America; Center for Biomedical Research, The Burnet Institute, Melbourne, Australia.
5
Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom.
6
Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom; Infectious Disease Research Collaboration, Uganda.
7
Infectious Disease Research Collaboration, Uganda.
8
Infectious Disease Research Collaboration, Uganda; Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda.

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.

PMID:
25993340
PMCID:
PMC4438005
DOI:
10.1371/journal.ppat.1004894
[Indexed for MEDLINE]
Free PMC Article

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