Productive infection of normal CD40-activated human B lymphocytes by HIV-1.
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.


CONCLUSIONS
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.
Poulin
L
L
Department of Microbiology, Laval University, Quebec, Canada.
Paquette
N
N
Moir
S
S
Lapointe
R
R
Darveau
A
A
D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004279:DNA, Viral / Q000032:analysis / Q000096:biosynthesis; D005455:Fluorescent Antibody Technique; D015752:Genes, env; D015750:Genes, gag; D015751:Genes, pol; D018023:HIV Seronegativity / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D014779:Virus Replication
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D004279:DNA, Viral; D004247:DNA