title: Evidence of early B-cell dysregulation in simian immunodeficiency virus infection: rapid depletion of naïve and memory B-cell subsets with delayed reconstitution of the naïve B-cell population.
abstract: Despite eliciting a robust antibody response in humans, several studies in human immunodeficiency virus (HIV)-infected patients have demonstrated the presence of B-cell deficiencies during the chronic stage of infection. While several explanations for the HIV-induced B-cell deficit have been proposed, a clear mechanistic understanding of this loss of B-cell functionality is not known. This study utilizes simian immunodeficiency virus (SIV) infection of rhesus macaques to assess B-cell population dynamics beginning at the acute phase and continuing through the chronic phase of infection. Flow cytometric assessment demonstrated a significant early depletion of both naïve and memory B-cell subsets in the peripheral blood, with differential kinetics for recovery of these populations. Furthermore, the altered numbers of naïve and memory B-cell subsets in these animals corresponded with increased B-cell activation and altered proliferation profiles during the acute phase of infection. Finally, all animals produced high titers of antibody, demonstrating that the measurement of virus-specific antibody responses was not an accurate reflection of alterations in the B-cell compartment. These data indicate that dynamic B-cell population changes in SIV-infected macaques arise very early after infection at the precise time when an effective adaptive immune response is needed.
authors.affiliation: Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: David
authors.initials: D
authors.lastname: Kuhrt
authors.forename: Seth A
authors.initials: SA
authors.lastname: Faith
authors.forename: Amanda
authors.initials: A
authors.lastname: Leone
authors.forename: Mukta
authors.initials: M
authors.lastname: Rohankedkar
authors.forename: Donald L
authors.initials: DL
authors.lastname: Sodora
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Picker
authors.forename: Kelly Stefano
authors.initials: KS
authors.lastname: Cole
mesh_terms: D056704:Adaptive Immunity / Q000502:physiology; D000818:Animals; D018951:Antigens, CD20 / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000821:virology; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D006801:Humans; D007072:Immunoglobulin D / Q000276:immunology; D008253:Macaca mulatta / Q000276:immunology / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology; D019562:Viral Load; D019014:fas Receptor / Q000276:immunology
chemical_list: D018951:Antigens, CD20; D007072:Immunoglobulin D; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D019014:fas Receptor