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

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.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

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

doi

10.1371/journal.ppat.1004894

subject

Has Abstract

pub_date

2015-05-19 00:00:00

pages

e1004894

issue

5

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-15-00243

journal_volume

11

pub_type

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