The Journal of Experimental Medicine
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Published online 5 September 2000.
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© The Rockefeller University Press, 0022-1007/2000/9/637/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 5, September 5, 2000 637-646


Original Article

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

Susan Moira, Angela Malaspinaa, Yuexia Lib, Tae-Wook Chuna, Tomeka Lowea, Joseph Adelsbergerc, Michael Baselerc, Linda A. Ehlera, Shuying Liua, Richard T. Davey, Jr.a, Jo Ann M. Micana, and Anthony S. Faucia

a Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892
b Advanced BioScience Laboratories, Incorporated, Kensington, Maryland 20895
c Science Applications International Corporation/Frederick, National Cancer Institute-Frederick Cancer and Development Center, Frederick, Maryland 21702
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg. 10, Rm. 6A02, Bethesda, MD 20892.301-402-4122301-402-4559

smoir{at}niaid.nih.gov

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.

Key Words: HIV-1 • B cell • viral reservoir • complement • CD21


Abbreviations used in this paper: DCs, dendritic cells; FDCs, follicular dendritic cells; ICs, immune complexes; NASBA, nucleic acid sequence–based amplification.

S. Moir and A. Malaspina contributed equally to this paper.

Yuexia Li's present address is VIRxSYS, Inc., Gaithersburg, MD 20877.

© 2000 The Rockefeller University Press


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