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

PLoS Pathogens

Chris J. Drakeley¹  Isaac Ssewanyana²  Felistas Nankya²  Charles C. Kim³  Mary F. Fontana³  Michelle J. Boyle³  Margaret E. Feeney³  Prasanna Jagannathan⁴  Richard T. Sullivan⁵  Harriet Mayanja-Kizza⁶  Grant Dorsey⁶  Bryan Greenhouse⁶ 

[1] Center for Biomedical Research, The Burnet Institute, Melbourne, Australia;Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom;Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California, United States of America;Division of HIV/AIDS, Department of Medicine, University of California, San Francisco, San Francisco, California, United States of America;Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, San Francisco, California, United States of America;Infectious Disease Research Collaboration, Uganda

关键词: B cells;    Antibody production;    Plasmodium;    Cloning;    Memory B cells;    Enzyme-linked immunoassays;    Malaria;    Gene expression;   

DOI  :  10.1371/journal.ppat.1004894

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY