title: Two overrepresented B cell populations in HIV-infected individuals undergo apoptosis by different mechanisms.
abstract: Perturbations of B cells in HIV-infected individuals are associated with the overrepresentation of distinct B cell populations. Here we describe high extrinsic CD95 ligand (CD95L)-mediated apoptosis in CD10-/CD21lo mature/activated B cells that likely arise from HIV-induced immune activation. In addition, high intrinsic apoptosis was observed in CD10+ immature/transitional B cells that likely arise as a result of HIV-induced lymphopenia. CD10+ B cells expressed low levels of Bcl-2 and Bcl-xL, consistent with their high susceptibility to intrinsic apoptosis. Higher levels of activated Bax and Bak were induced in CD10+ B cells compared with CD95L-treated CD10- B cells, consistent with the greater involvement of mitochondria in intrinsic vs. extrinsic apoptosis. Of interest, both extrinsic apoptosis in CD95L-treated CD10- B cells and intrinsic apoptosis in CD10+ B cells were associated with caspase-8 activation. Our data suggest that two distinct mechanisms of apoptosis are associated with B cells of HIV-infected individuals, and both may contribute to the depletion and dysfunction of B cells in these individuals.
authors.affiliation: Laboratory of Immunoregulation and Office of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Ho
authors.forename: Susan
authors.initials: S
authors.lastname: Moir
authors.forename: Angela
authors.initials: A
authors.lastname: Malaspina
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Howell
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Angela C
authors.initials: AC
authors.lastname: DiPoto
authors.forename: Marie A
authors.initials: MA
authors.lastname: O'Shea
authors.forename: Gregg A
authors.initials: GA
authors.lastname: Roby
authors.forename: Richard
authors.initials: R
authors.lastname: Kwan
authors.forename: JoAnn M
authors.initials: JM
authors.lastname: Mican
authors.forename: Tae-Wook
authors.initials: TW
authors.lastname: Chun
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Fauci
mesh_terms: D017209:Apoptosis / Q000276:immunology / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D053181:Caspase 8 / Q000276:immunology; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D015260:Neprilysin / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism; D019014:fas Receptor / Q000276:immunology
chemical_list: C494772:BAK1 protein, human; C494811:BCL2L1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019014:fas Receptor; D053181:Caspase 8; D015260:Neprilysin