title: Primary human cytomegalovirus infection induces the expansion of virus-specific activated and atypical memory B cells.
abstract: BACKGROUND
  Although neutralizing antibodies play a central role in the control of cytomegalovirus (CMV) dissemination, little is known about the response of B lymphocytes to primary human CMV infection.
  
  
  METHODS
  The proportion, phenotype, specificity, and functionality of B-cell subsets were studied in a cohort of pregnant women with primary CMV infection. CMV-seronegative pregnant women, as well as CMV-seronegative and CMV-seropositive healthy adults, were included as controls.
  
  
  RESULTS
  Primary CMV infection was associated with a sustained expansion of activated (CD27(+)CD20(+)CD21(low)) and atypical (CD27(-)CD20(+)CD21(low)) memory B cells (MBCs). Both subsets expressed an effector phenotype, and their proportions were correlated with viremia. Activated MBCs expressed high levels of activation markers and included high frequencies of tumor necrosis α (TNF-α)-producing cells, whereas atypical MBCs expressed high levels of inhibitory receptors and had low TNF-α responses. Fluorescent-labeled antigen experiments indicated that activated and atypical MBCs were enriched in CMV-specific cells.
  
  
  CONCLUSIONS
  Primary CMV infection mobilizes a large pool of memory B cells that includes activated and atypical MBCs. The functional regulation of CMV-specific MBCs may limit the production of antibodies and the control of viral dissemination.
authors.affiliation: Institute for Medical Immunology, Université Libre de Bruxelles (ULB).
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dauby
authors.affiliation: ImmuneHealth, Gosselies.
authors.forename: Caroline
authors.initials: C
authors.lastname: Kummert
authors.affiliation: Institute for Medical Immunology, Université Libre de Bruxelles (ULB).
authors.forename: Sandra
authors.initials: S
authors.lastname: Lecomte
authors.affiliation: Department of Virology.
authors.forename: Corinne
authors.initials: C
authors.lastname: Liesnard
authors.affiliation: Department of Virology.
authors.forename: Marie-Luce
authors.initials: ML
authors.lastname: Delforge
authors.affiliation: Department of Obstetrics and Gynecology, Hôpital Erasme, ULB, Brussels, Belgium.
authors.forename: Catherine
authors.initials: C
authors.lastname: Donner
authors.affiliation: Institute for Medical Immunology, Université Libre de Bruxelles (ULB) ImmuneHealth, Gosselies.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Marchant
mesh_terms: D000328:Adult; D016175:B-Lymphocyte Subsets / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000821:virology
keywords: activated memory B cells; atypical memory B cells; cytomegalovirus; primary infection