title: High expression levels of BLyS/BAFF by blood dendritic cells and granulocytes are associated with B-cell dysregulation in SIV-infected rhesus macaques.
abstract: Dendritic cells (DCs) modulate B-cell survival and differentiation, mainly through production of growth factors such as B lymphocyte stimulator (BLyS/BAFF). In recent longitudinal studies involving HIV-1-infected individuals with different rates of disease progression, we have shown that DCs were altered in number and phenotype in the context of HIV-1 disease progression and B-cell dysregulations were associated with increased BLyS/BAFF expression in plasma and by blood myeloid DCs (mDCs) in rapid and classic progressors but not in HIV-1-elite controllers (EC). Suggesting that the extent to which HIV-1 disease progression is controlled may be linked to BLyS/BAFF expression status and the capacity to orchestrate B-cell responses. Herein, longitudinal analyses of simian immunodeficiency virus (SIV)-infected rhesus macaques also revealed increased expression of BLyS/BAFF by blood mDCs as soon as day 8 and throughout infection. Strikingly, granulocytes presented the highest BLyS/BAFF expression profile in the blood of SIV-infected macaques. BLyS/BAFF levels were also increased in plasma and correlated with viral loads. Consequently, these SIV-infected animals had plasma hyperglobulinemia and reduced blood B-cell numbers with altered population frequencies. These data underscore that BLyS/BAFF is associated with immune dysregulation in SIV-infected rhesus macaques and suggest that BLyS/BAFF is a key regulator of immune activation that is highly conserved among primates. These findings emphasize the potential importance of this SIV-infected primate model to test whether blocking excess BLyS/BAFF has an effect on the overall inflammatory burden and immune restoration.
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: Boston College, Boston, MA, United States of America.
authors.forename: Caroline
authors.initials: C
authors.lastname: Soulas
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: Boston College, Boston, MA, United States of America.
authors.forename: Tricia
authors.initials: T
authors.lastname: Burdo
authors.affiliation: Boston College, Boston, MA, United States of America.
authors.forename: Patrick
authors.initials: P
authors.lastname: Autissier
authors.affiliation: Boston College, Boston, MA, United States of America.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Oskar
authors.affiliation: Boston College, Boston, MA, United States of America.
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Williams
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: D000818:Animals; D053264:B-Cell Activating Factor / Q000097:blood*; D001402:B-Lymphocytes / Q000166:cytology* / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000821:virology; D002454:Cell Differentiation; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology* / Q000821:virology; D018450:Disease Progression; D005434:Flow Cytometry; D006098:Granulocytes / Q000166:cytology* / Q000821:virology; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007249:Inflammation; D008253:Macaca mulatta; D008297:Male; D010641:Phenotype; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood* / Q000821:virology; D015302:Simian Immunodeficiency Virus; D019562:Viral Load
chemical_list: D053264:B-Cell Activating Factor; D007074:Immunoglobulin G; D007075:Immunoglobulin M