title: Fluctuations in Blood Marginal Zone B-Cell Frequencies May Reflect Migratory Patterns Associated with HIV-1 Disease Progression Status.
abstract: We have previously shown that overexpression of BLyS/BAFF was associated with increased relative frequencies of innate "precursor" marginal zone (MZ)-like B-cells in the blood of HIV-1-infected rapid and classic progressors. However, along with relatively normal BLyS/BAFF expression levels, these cells remain unaltered in elite-controllers (EC), rather, percentages of more mature MZ-like B-cells are decreased in the blood of these individuals. Fluctuations in frequencies of blood MZ-like B-cell populations may reflect migratory patterns associated with disease progression status, suggesting an important role for these cells in HIV-1 pathogenesis. We have therefore longitudinally measured plasma levels of B-tropic chemokines by ELISA-based technology as well as their ligands by flow-cytometry on blood B-cell populations of HIV-1-infected individuals with different rates of disease progression and uninfected controls. Migration potential of B-cell populations from these individuals were determined by chemotaxis assays. We found important modulations of CXCL13-CXCR5, CXCL12-CXCR4/CXCR7, CCL20-CCR6 and CCL25-CCR9 chemokine-axes and increased cell migration patterns in HIV progressors. Interestingly, frequencies of CCR6 expressing cells were significantly elevated within the precursor MZ-like population, consistent with increased migration in response to CCL20. Although we found little modulation of chemokine-axes in EC, cell migration was greater than that observed for uninfected controls, especially for MZ-like B-cells. Overall the immune response against HIV-1 may involve recruitment of MZ-like B-cells to peripheral sites. Moreover, our findings suggest that "regulated" attraction of these cells in a preserved BLyS/BAFF non-inflammatory environment, such as encountered in EC could be beneficial to the battle and even control of HIV.
authors.affiliation: Laboratoire d'immunogénétique, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Canada.|Département de Microbiologie, Infectiologie et Immunologie de l'Université de Montréal, Montréal, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Gauvin
authors.affiliation: Laboratoire d'immunogénétique, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Canada.|Département de Microbiologie, Infectiologie et Immunologie de l'Université de Montréal, Montréal, Canada.
authors.forename: Josiane
authors.initials: J
authors.lastname: Chagnon-Choquet
authors.affiliation: Laboratoire d'immunogénétique, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Canada.|Département de Microbiologie, Infectiologie et Immunologie de l'Université de Montréal, Montréal, Canada.
authors.forename: Johanne
authors.initials: J
authors.lastname: Poudrier
authors.affiliation: Laboratoire d'immunogénétique, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Canada.|Département de Microbiologie, Infectiologie et Immunologie de l'Université de Montréal, Montréal, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Roger
mesh_terms: D000328:Adult; D053264:B-Cell Activating Factor / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism*; D054377:Chemokine CXCL12 / Q000097:blood; D054382:Chemokine CXCL13 / Q000097:blood; D019742:Chemokines, CC / Q000097:blood; D002633:Chemotaxis / Q000502:physiology; D018450:Disease Progression; D015658:HIV Infections / Q000097:blood* / Q000473:pathology*; D015497:HIV-1 / Q000472:pathogenicity; D006801:Humans; D019718:Receptors, CXCR4 / Q000097:blood; D012959:Socioeconomic Factors; D055815:Young Adult
chemical_list: D053264:B-Cell Activating Factor; C108074:CCL25 protein, human; C515255:CXCL12 protein, human; C110663:CXCL13 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D019742:Chemokines, CC; D019718:Receptors, CXCR4; C505719:TNFSF13B protein, human