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

J Alzheimers Dis. 2015;44(4):1241-51. doi: 10.3233/JAD-142412.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / immunology*
  • Alzheimer Disease / pathology*
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / pathology*
  • Cohort Studies
  • Female
  • Flow Cytometry
  • Humans
  • Immunoglobulin D
  • Immunoglobulin G
  • Male
  • Mental Status Schedule
  • Phenotype
  • Receptors, CCR6 / metabolism*
  • Receptors, CCR7 / metabolism*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology

Substances

  • CCR6 protein, human
  • CCR7 protein, human
  • Immunoglobulin D
  • Immunoglobulin G
  • Receptors, CCR6
  • Receptors, CCR7
  • Tumor Necrosis Factor Receptor Superfamily, Member 7