title: Double negative (IgG+IgD-CD27-) B cells are increased in a cohort of moderate-severe Alzheimer's disease patients and show a pro-inflammatory trafficking receptor phenotype.
abstract: Alzheimer's disease (AD) is a progressive, irreversible, and debilitating disease for which no effective preventive or disease modifying therapies or treatments have so far been detected. The crucial step in AD pathogenesis is the production of amyloid-β42 peptide, which causes chronic inflammation. Activated cells in the central nervous system (CNS) produce pro-inflammatory mediators that lead to the recruitment of myeloid or lymphocytic cells. As a consequence, the communication between the CNS and peripheral blood of AD subjects could influence the lymphocyte distribution and/or the expression of phenotypic markers. In the present paper, we show a significant decrease in total CD19+ B lymphocytes and a remodeling of the B cell subpopulations in moderate-severe AD patients, compared with their coeval healthy controls and mild AD subjects. In particular, we report a significant reduction in naïve B cells (IgD+CD27-) and a simultaneous increase in double negative (DN, IgD-CD27-) memory B lymphocytes. We have also evaluated the expression of the pro-inflammatory chemokine receptors CCR6 and CCR7 in total and naïve/memory B cells from mild and moderate-severe AD patients, with the aim to detect a possible relationship between the trafficking profile and the stage of the disease. Our results demonstrate that both the amount and the trafficking profile of B cells are related to the severity of AD. The results discussed in this paper suggest a well-selected antibody panel should be used as an additional test for the identification of early AD.
authors.affiliation: Immunosenescence Unit, Department of Pathobiology and Medical and Forensic Biotechnologies (DIBIMEF), University of Palermo, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Bulati
authors.affiliation: Immunosenescence Unit, Department of Pathobiology and Medical and Forensic Biotechnologies (DIBIMEF), University of Palermo, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Buffa
authors.affiliation: Immunosenescence Unit, Department of Pathobiology and Medical and Forensic Biotechnologies (DIBIMEF), University of Palermo, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Martorana
authors.affiliation: Laboratory of experimental Oncohematology and cell cultures for clinical use, ARNAS CIVICO, Palermo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Gervasi
authors.affiliation: Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Camarda
authors.affiliation: Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Italy.
authors.forename: Delia Maria
authors.initials: DM
authors.lastname: Azzarello
authors.affiliation: Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Monastero
authors.affiliation: Immunosenescence Unit, Department of Pathobiology and Medical and Forensic Biotechnologies (DIBIMEF), University of Palermo, Italy.
authors.forename: Calogero
authors.initials: C
authors.lastname: Caruso
authors.affiliation: Immunosenescence Unit, Department of Pathobiology and Medical and Forensic Biotechnologies (DIBIMEF), University of Palermo, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Colonna-Romano
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000276:immunology* / Q000473:pathology*; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007072:Immunoglobulin D; D007074:Immunoglobulin G; D008297:Male; D008609:Mental Status Schedule; D010641:Phenotype; D054399:Receptors, CCR6 / Q000378:metabolism*; D054400:Receptors, CCR7 / Q000378:metabolism*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology
chemical_list: C106311:CCR6 protein, human; C515370:CCR7 protein, human; D007072:Immunoglobulin D; D007074:Immunoglobulin G; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
keywords: Aging; Alzheimer's disease; B cells; CCR6; CCR7; trafficking profile