title: 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.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Sullivan
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Kim
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Mary F
authors.initials: MF
authors.lastname: Fontana
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Feeney
authors.affiliation: Division of HIV/AIDS, Department of Medicine, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Prasanna
authors.initials: P
authors.lastname: Jagannathan
authors.affiliation: 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.
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Boyle
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Drakeley
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom; Infectious Disease Research Collaboration, Uganda.
authors.forename: Isaac
authors.initials: I
authors.lastname: Ssewanyana
authors.affiliation: Infectious Disease Research Collaboration, Uganda.
authors.forename: Felistas
authors.initials: F
authors.lastname: Nankya
authors.affiliation: Infectious Disease Research Collaboration, Uganda; Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Harriet
authors.initials: H
authors.lastname: Mayanja-Kizza
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Grant
authors.initials: G
authors.lastname: Dorsey
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Bryan
authors.initials: B
authors.lastname: Greenhouse
mesh_terms: D000328:Adult; D000818:Animals; D000953:Antigens, Protozoan / Q000378:metabolism; D058070:Asymptomatic Diseases / Q000453:epidemiology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D017028:Caregivers; D002460:Cell Line; D002478:Cells, Cultured; D002648:Child; D015331:Cohort Studies; D019353:Endemic Diseases; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007156:Immunologic Memory; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D010963:Plasmodium falciparum / Q000276:immunology*; D011961:Receptors, Fc / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014454:Uganda / Q000453:epidemiology
chemical_list: D000953:Antigens, Protozoan; C423544:FCRL4 protein, human; C432367:FCRL5 protein, human; D011961:Receptors, Fc; D011994:Recombinant Proteins