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

Front Immunol. 2021 Jan 15:11:614319. doi: 10.3389/fimmu.2020.614319. eCollection 2020.

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.

Keywords: B-cell activation; PD-1; marginal zone (MZ) B cell; plasmablasts; transitional B cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • HIV Infections / immunology*
  • HIV Infections / pathology
  • HIV Infections / 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

Substances

  • Anti-Retroviral Agents
  • Cytokines
  • Immunoglobulin D
  • Immunoglobulin G
  • Immunoglobulin M
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor