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
Affiliations: [a] Immunosenescence Unit, Department of Pathobiology and Medical and Forensic Biotechnologies (DIBIMEF), University of Palermo, Italy | [b] Laboratory of experimental Oncohematology and cell cultures for clinical use, ARNAS CIVICO, Palermo, Italy | [c] Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Italy
Correspondence:
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Correspondence to: Giuseppina Colonna-Romano, Immunosenescence Unit, Department of Pathobiology and Medical and Forensic Biotechnologies (DIBIMEF), University of Palermo, Corso Tukory 211, 90134 Palermo, Italy. Tel.: +39 0916555906; Fax: +39 0916555933; E-mail: [email protected].
Note: [1] These authors contributed equally to this work.
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.
Keywords: Aging, Alzheimer's disease, B cells, CCR6, CCR7, trafficking profile
