title: Down-regulation of CD73 on B cells of patients with viremic HIV correlates with B cell activation and disease progression.
abstract: Recently, alterations of the T cell expression of the ectonucleotidases, CD39 and CD73, during HIV infection have been described. Here, peripheral (n= 70) and lymph nodal B cells (n= 10) of patients with HIV at different stages of disease as well as uninfected individuals were analyzed via multicolor flow cytometry with regard to expression of CD39 and CD73 and differentiation, proliferation, and exhaustion status. Patients with chronic, untreated HIV showed a significantly decreased frequency of CD73-expressing B cells (P< 0.001) compared with healthy controls. Decreased frequencies of CD39+CD73+B cells in patients with HIV correlated with low CD4+counts (P< 0.0256) as well as increased proliferation and exhaustion status as determined by Ki-67 and programmed death-1 expression. Down-regulation of CD73 was observed in naive and memory B cells as determined by CD27 and CD21. Neither HIV elite controller patients nor antiretroviral therapy-treated patients had significantly lower CD39 and CD73 expression on B cells compared with healthy controls. Of importance, low CD73+expression on B cells was associated with modulated in vitro B cell function. Further in vivo studies are warranted to evaluate the in vivo role of phenotypic loss of CD73 in B cell dysregulation in HIV.
authors.affiliation: I. Department of Medicine, Section of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany.
authors.forename: Eun-Seong
authors.initials: ES
authors.lastname: Kim
authors.affiliation: I. Department of Medicine, Section of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany.
authors.forename: Christin
authors.initials: C
authors.lastname: Ackermann
authors.affiliation: I. Department of Medicine, Section of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany.
authors.forename: Ilona
authors.initials: I
authors.lastname: Tóth
authors.affiliation: I. Department of Medicine, Section of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Dierks
authors.affiliation: I. Department of Medicine, Section of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany.|German Center for Infection Research, Hamburg, Hannover, Germany.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Eberhard
authors.affiliation: I. Department of Medicine, Section of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany.|German Center for Infection Research, Hamburg, Hannover, Germany.
authors.forename: Raluca
authors.initials: R
authors.lastname: Wroblewski
authors.affiliation: Department of Immunology, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Scherg
authors.affiliation: Center of Advanced European Studies and Research, Bonn, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Geyer
authors.affiliation: German Center for Infection Research, Hamburg, Hannover, Germany.|Center for Immunology and Rheumatology, Hannover Medical School, Hannover, Germany.
authors.forename: Reinhold E
authors.initials: RE
authors.lastname: Schmidt
authors.affiliation: I. Department of Medicine, Section of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany.|German Center for Infection Research, Hamburg, Hannover, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Beisel
authors.affiliation: Department of General Surgery, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Bockhorn
authors.affiliation: Department of Immunology, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Haag
authors.affiliation: Viiv Healthcare, London, United Kingdom.
authors.forename: Jan
authors.initials: J
authors.lastname: van Lunzen
authors.affiliation: I. Department of Medicine, Section of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany; julianszw@gmail.com.|German Center for Infection Research, Hamburg, Hannover, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Schulze Zur Wiesch
mesh_terms: D015720:5'-Nucleotidase / Q000235:genetics / Q000276:immunology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D001081:Apyrase / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D002454:Cell Differentiation; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006801:Humans; D007156:Immunologic Memory; D019394:Ki-67 Antigen / Q000235:genetics / Q000276:immunology; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000821:virology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000276:immunology; D017464:Receptors, Complement 3d / Q000235:genetics / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics / Q000276:immunology; D014766:Viremia / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000821:virology
chemical_list: D019380:Anti-HIV Agents; D015703:Antigens, CD; D058851:GPI-Linked Proteins; D019394:Ki-67 Antigen; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D017464:Receptors, Complement 3d; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D015720:5'-Nucleotidase; C548241:NT5E protein, human; D001081:Apyrase; C067869:CD39 antigen
keywords: 5′-ectonucleotidase; ADO; CD39; Ig class switch; elite controller