title: Control of Viremia Enables Acquisition of Resting Memory B Cells with Age and Normalization of Activated B Cell Phenotypes in HIV-Infected Children.
abstract: HIV affects the function of all lymphocyte populations, including B cells. Phenotypic and functional defects of B cells in HIV-infected adults have been well characterized, but defects in children have not been studied to the same extent. We determined the proportion of B cell subsets and frequencies of Ag-specific memory B cells in peripheral blood from HIV-infected children and healthy controls, using flow cytometry and B cell ELISPOT, respectively. In addition, we measured the quantities and avidities of plasma Abs against various Ags by ELISA. We also determined plasma levels of BAFF and expression of BAFF receptors on B cells. Children with high HIV viremia had increased proportions of activated mature B cells, tissue-like memory B cells and plasmablasts, and low proportions of naive B cells when compared with community controls and children with low HIV viremia, similar to adults infected with HIV. HIV-infected groups had lower proportions of resting memory B cells than did community controls. Notably, high HIV viremia prevented the age-dependent accumulation of class-switched resting memory B cells. HIV-infected children, regardless of the level of viremia, showed lower quantities and avidities of IgG and lower frequencies of memory B cells against Expanded Program on Immunization vaccines. The HIV-infected children had an altered BAFF profile that could have affected their B cell compartment. Therefore, B cell defects in HIV-infected children are similar to those seen in HIV-infected adults. However, control of HIV viremia is associated with normalization of activated B cell subsets and allows age-dependent accumulation of resting memory B cells.
authors.affiliation: Kenya Medical Research Institute-Wellcome Trust Research Programme, Centre for Geographic Research - Coast, 80108 Kilifi, Kenya;
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Muema
authors.affiliation: Kenya Medical Research Institute-Wellcome Trust Research Programme, Centre for Geographic Research - Coast, 80108 Kilifi, Kenya;
authors.forename: Gladys N
authors.initials: GN
authors.lastname: Macharia
authors.affiliation: Kenya Medical Research Institute-Wellcome Trust Research Programme, Centre for Geographic Research - Coast, 80108 Kilifi, Kenya;
authors.forename: Amin S
authors.initials: AS
authors.lastname: Hassan
authors.affiliation: Kenya Medical Research Institute-Wellcome Trust Research Programme, Centre for Geographic Research - Coast, 80108 Kilifi, Kenya;
authors.forename: Shalton M
authors.initials: SM
authors.lastname: Mwaringa
authors.affiliation: Kenya Medical Research Institute-Wellcome Trust Research Programme, Centre for Geographic Research - Coast, 80108 Kilifi, Kenya; Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford OX3 7LJ, United Kingdom; and.
authors.forename: Greg W
authors.initials: GW
authors.lastname: Fegan
authors.affiliation: Kenya Medical Research Institute-Wellcome Trust Research Programme, Centre for Geographic Research - Coast, 80108 Kilifi, Kenya; Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford OX3 7LJ, United Kingdom; and.
authors.forename: James A
authors.initials: JA
authors.lastname: Berkley
authors.affiliation: Kenya Medical Research Institute-Wellcome Trust Research Programme, Centre for Geographic Research - Coast, 80108 Kilifi, Kenya; enduati@kemri-wellcome.org.
authors.forename: Eunice W
authors.initials: EW
authors.lastname: Nduati
authors.affiliation: Kenya Medical Research Institute-Wellcome Trust Research Programme, Centre for Geographic Research - Coast, 80108 Kilifi, Kenya; Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kingdom.
authors.forename: Britta C
authors.initials: BC
authors.lastname: Urban
mesh_terms: D000915:Antibody Affinity / Q000276:immunology; D053264:B-Cell Activating Factor / Q000097:blood*; D053265:B-Cell Activation Factor Receptor / Q000096:biosynthesis / Q000378:metabolism*; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D002675:Child, Preschool; D005260:Female; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D014766:Viremia / Q000276:immunology* / Q000821:virology
chemical_list: D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D015483:HIV Antibodies; D007074:Immunoglobulin G; C435926:TNFRSF13C protein, human; C505719:TNFSF13B protein, human