B Cells of HIV-1–Infected Patients Bind Virions through Cd21–Complement Interactions and Transmit Infectious Virus to Activated T Cells

Author:

Moir Susan1,Malaspina Angela1,Li Yuexia2,Chun Tae-Wook1,Lowe Tomeka1,Adelsberger Joseph3,Baseler Michael3,Ehler Linda A.1,Liu Shuying1,Davey Richard T.1,Mican Jo Ann M.1,Fauci Anthony S.1

Affiliation:

1. Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892

2. Advanced BioScience Laboratories, Incorporated, Kensington, Maryland 20895

3. Science Applications International Corporation/Frederick, National Cancer Institute-Frederick Cancer and Development Center, Frederick, Maryland 21702

Abstract

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.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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