Pathogenic mechanisms of B-lymphocyte dysfunction in HIV disease

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Presentation transcript:

Pathogenic mechanisms of B-lymphocyte dysfunction in HIV disease Susan Moir, PhD, Anthony S. Fauci, MD Journal of Allergy and Clinical Immunology Volume 122, Issue 1, Pages 12-19 (July 2008) DOI: 10.1016/j.jaci.2008.04.034 Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Phenotypic and genotypic aberrancies associated with HIV viremia. A, Phenotypic profile of peripheral blood–derived B cells isolated from representative HIV-negative and HIV-viremic individuals illustrating decreased CD21 expression on B cells of the HIV-viremic individual. B, Electron micrograph illustrating presence of cells with plasmacytoid features in the CD21lo B-cell fraction of a representative HIV-viremic individual. Micrograph originally appeared in Moir S, Malaspina A, Ogwaro KM, Donoghue ET, Hallahan CW, Ehler LA, et al. HIV-1 induces phenotypic and functional perturbations of B cells in chronically infected individuals. Proc Natl Acad Sci U S A 2001;98:10362-7.9C, Main findings from DNA microarray analyses performed on blood-derived B cells isolated from HIV-viremic individuals and compared with B cells isolated from HIV-aviremic and HIV-negative individuals.18BCMA, B-cell maturation protein; IFI, IFN-induced family of genes; ISG, IFN-stimulated gene. Journal of Allergy and Clinical Immunology 2008 122, 12-19DOI: (10.1016/j.jaci.2008.04.034) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 HIV disease is associated with increased B-cell turnover and increased B-cell death by intrinsic and extrinsic apoptosis. A, Identification of B-cell subpopulations in the peripheral blood of a representative HIV-infected individual with active disease. B, Increased expression of CD95 on CD10-/CD21lo mature/activated B cells correlates with increased susceptibility to CD95-mediated extrinsic apoptosis. C, CD10-/CD21lo mature/activated B cells also express increased levels of the cell-cycling marker Ki-67. Decreased expression of (D) Bcl-2 and (E) Bcl-xL in CD10+ immature/transitional B cells is associated with increased susceptibility to intrinsic apoptosis. These profiles originally appeared in Ho J, Moir S, Malaspina A, Howell ML, Wang W, DiPoto AC, et al. Two overrepresented B cell populations in HIV-infected individuals undergo apoptosis by different mechanisms. Proc Natl Acad Sci U S A 2006;103:19436-41.48Max, Maximum. Journal of Allergy and Clinical Immunology 2008 122, 12-19DOI: (10.1016/j.jaci.2008.04.034) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions