Journal
PLOS PATHOGENS
Volume 11, Issue 5, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.1004894
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Funding
- National Institutes of Health [R00 AI085035, R21 AI107200, R01AI093615]
- National Institutes of Health International Centers of Excellence in Malaria Research (ICMER) program [U19AI089674]
- National Institutes of Health/National Institute of Allergy and Infectious Disease [K23 AI100949]
- Burroughs Wellcome Fund/American Society of Tropical Medicine and Hygiene
- University of California San Francisco Centers for AIDS Research [P30AI027763]
- National Health and Medical Research Council Australian Early-Career Fellowship
- National Health and Research Council Infrastructure for Research Institutes Support Scheme and Victoria State Government Operational Infrastructure Support
- National Center for Advancing Translational Sciences, National Institutes of Health through University of California San Francisco Clinical Translational Science Institute [UL1 TR000004]
- Doris Duke Charitable Foundation
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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.
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