B cells of HIV-1-infected patients bind virions through CD21-complement interactions and transmit infectious virus to activated T cells.
The impact of HIV-associated immunopathogenesis on B cells has been largely associated with indirect consequences of viral replication. This study demonstrates that HIV interacts directly with B cells in both lymphoid tissues and peripheral blood. B cells isolated from lymph node and peripheral blood mononuclear cells (PBMCs) of 4 and 23 chronically infected patients, respectively, demonstrated similar capacities to pass virus to activated HIV-negative PBMCs when compared with CD4(+) cells from the same patients. However, in contrast to T cells, virus associated with B cells was surface bound, as shown by its sensitivity to pronase and the staining pattern revealed by in situ amplification of HIV-1 RNA. Cell sorting and ligand displacing approaches established that CD21 was the HIV-binding receptor on B cells, and that this association was mediated through complement-opsonized virus. These B cells were also found to express significantly lower levels of CD21 compared with HIV-negative individuals, suggesting a direct perturbing effect of HIV on B cells. These findings suggest that B cells, although they themselves are not readily infected by HIV, are similar to follicular dendritic cells in their capacity to serve as extracellular reservoirs for HIV-1. Furthermore, B cells possess the added capability of circulating in peripheral blood and migrating through tissues where they can potentially interact with and pass virus to T cells.
Moir
S
S
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. smoir@niaid.nih.gov
Malaspina
A
A
Li
Y
Y
Chun
T W
TW
Lowe
T
T
Adelsberger
J
J
Baseler
M
M
Ehler
L A
LA
Liu
S
S
Davey
R T
RT
Mican
J A
JA
Fauci
A S
AS
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000821:virology*; D002908:Chronic Disease; D003176:Complement C3 / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D012367:RNA, Viral / Q000032:analysis; D017464:Receptors, Complement 3d / Q000502:physiology*; D013601:T-Lymphocytes / Q000821:virology*; D014771:Virion / Q000502:physiology*
D000911:Antibodies, Monoclonal; D003176:Complement C3; D012367:RNA, Viral; D017464:Receptors, Complement 3d