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

• Published in: Frontiers in immunology 2021-01, Vol.11, p.614319-614319
• Main Authors: Jiménez, Montse, Pastor, Lucía, Urrea, Victor, Rodríguez de la Concepción, María Luisa, Parker, Erica, Fuente-Soro, Laura, Jairoce, Chenjerai, Mandomando, Inacio, Carrillo, Jorge, Naniche, Denise, Blanco, Julià
• Format: Article
• Language: English
• Subjects: B-cell activation; Immunology; marginal zone (MZ) B cell; PD-1; plasmablasts; transitional B cell
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2020.614319

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.