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; (2015) FCRL5 Delineates Functionally Impaired Memory B Cells Associated with Plasmodium falciparum Exposure. PLoS pathogens, 11 (5). e1004894. ISSN 1553-7366 DOI: https://doi.org/10.1371/journal.ppat.1004894

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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.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Malaria Centre
PubMed ID: 25993340
Web of Science ID: 355269300038
URI: http://researchonline.lshtm.ac.uk/id/eprint/2173690

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