Productive Infection of Normal CD40-activated Human B Lymphocytes by HIV-1

AIDS. 1994 Nov;8(11):1539-44. doi: 10.1097/00002030-199411000-00004.

Abstract

Objective: Antigen-driven B-cell proliferation and maturation occur in germinal centres present in lymphoid tissues. This process is highly dependent on functional interactions between B and T lymphocytes. In vitro activation of CD40 present on B cells mimics B cell-T interactions and allows the proliferation of normal Epstein-Barr virus (EBV)-negative B lymphocytes. In HIV-1-seropositive individuals, B cells become exposed to free viral particles and to infected T lymphocytes while migrating through germinal centres. The effect of HIV-1 viral exposure on CD40-activated B lymphocytes was therefore examined.

Methods: Freshly isolated B lymphocytes were cultured in vitro through activation of CD40. B-cell proliferation, HIV-1 infectivity and viral production were monitored following B-lymphocyte exposure to HIV-1. In addition, HIV-mediated fusion between infected B cells and uninfected CD4+ T lymphocytes was assessed in a coculture assay.

Results: EBV-negative, CD40-activated human B lymphocytes were directly infected by HIV-1. The infection significantly reduced their proliferation rate. Viral production was detected in B-cell culture supernatant. Numerous fusion events indicated that HIV-1 infection of B lymphocytes could spread to T lymphocytes following HIV-1-mediated fusion of these two cell types.

Conclusion: In view of the importance of B cell-T cell interactions in the maintenance of a functional immune system, disruption of B-lymphocyte development could have direct implications on the course of AIDS progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / immunology*
  • Antigens, Differentiation, B-Lymphocyte / immunology*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / virology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD40 Antigens
  • Cells, Cultured
  • DNA / biosynthesis
  • DNA, Viral / analysis
  • DNA, Viral / biosynthesis
  • Fluorescent Antibody Technique
  • Genes, env
  • Genes, gag
  • Genes, pol
  • HIV Seronegativity / immunology
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • HIV-1 / physiology
  • Humans
  • Lymphocyte Activation
  • Polymerase Chain Reaction
  • T-Lymphocytes / immunology
  • Virus Replication

Substances

  • Antigens, CD
  • Antigens, Differentiation, B-Lymphocyte
  • CD40 Antigens
  • DNA, Viral
  • DNA