Nicolas Dauby1, Caroline Kummert2, Sandra Lecomte1, Corinne Liesnard3, Marie-Luce Delforge3, Catherine Donner4, Arnaud Marchant5. 1. Institute for Medical Immunology, Université Libre de Bruxelles (ULB). 2. ImmuneHealth, Gosselies. 3. Department of Virology. 4. Department of Obstetrics and Gynecology, Hôpital Erasme, ULB, Brussels, Belgium. 5. Institute for Medical Immunology, Université Libre de Bruxelles (ULB) ImmuneHealth, Gosselies.
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.
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 humanCMV 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.
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