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A Longitudinal Analysis Reveals Early Activation and Late Alterations in B Cells During Primary HIV Infection in Mozambican Adults.

Abstract
Primary HIV infection (PHI) and subsequent chronic infection alter B-cell compartment. However, longitudinal analysis defining the dynamics of B-cell alterations are still limited. We longitudinally studied B-cell subsets in individuals followed for 1 year after PHI (n = 40). Treated and untreated chronic HIV infected (n = 56) and HIV-uninfected individuals (n = 58) were recruited as reference groups at the Manhiça District in Mozambique. B cells were analyzed by multicolor flow-cytometry. Anti-HIV humoral response and plasma cytokines were assessed by ELISA or Luminex-based technology. A generalized activation of B cells induced by HIV occurs early after infection and is characterized by increases in Activated and Tissue-like memory cells, decreases in IgM-IgD- (switched) and IgM-only B cells. These alterations remain mostly stable until chronic infection and are reverted in part by ART. In contrast, other parameters followed particular dynamics: PD-1 expression in memory cells decreases progressively during the first year of infection, Transitional B cells expand at month 3-4 after infection, and Marginal zone-like B cells show a late depletion. Plasmablasts expand 2 months after infection linked to plasma viral load and anti-p24 IgG3 responses. Most of well-defined changes induced by HIV in B-cell activation and memory subsets are readily observed after PHI, lasting until ART initiation. However, subsequent changes occur after sustained viral infection. These data indicate that HIV infection impacts B cells in several waves over time, and highlight that early treatment would result in beneficial effects on the B-cell compartment.
AuthorsMontse Jiménez, Lucía Pastor, Victor Urrea, María Luisa Rodríguez de la Concepción, Erica Parker, Laura Fuente-Soro, Chenjerai Jairoce, Inacio Mandomando, Jorge Carrillo, Denise Naniche, Julià Blanco
JournalFrontiers in immunology (Front Immunol) Vol. 11 Pg. 614319 ( 2020) ISSN: 1664-3224 [Electronic] Switzerland
PMID33519823 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2021 Jiménez, Pastor, Urrea, Rodríguez de la Concepción, Parker, Fuente-Soro, Jairoce, Mandomando, Carrillo, Naniche and Blanco.
Chemical References
  • Anti-Retroviral Agents
  • Cytokines
  • Immunoglobulin D
  • Immunoglobulin G
  • Immunoglobulin M
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
Topics
  • Adult
  • Anti-Retroviral Agents (therapeutic use)
  • B-Lymphocyte Subsets (immunology)
  • B-Lymphocytes (immunology)
  • Chronic Disease
  • Cohort Studies
  • Cytokines (blood)
  • Flow Cytometry
  • HIV Infections (drug therapy, immunology, pathology, virology)
  • HIV-1 (immunology)
  • Humans
  • Immunity, Humoral
  • Immunoglobulin D (immunology)
  • Immunoglobulin G (immunology)
  • Immunoglobulin M (immunology)
  • Longitudinal Studies
  • Lymphocyte Activation
  • Mozambique (epidemiology)
  • Programmed Cell Death 1 Receptor (metabolism)
  • Prospective Studies
  • Viral Load

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