B Cells of HIV-1-infected Patients Bind Virions through CD21-Complement Interactions and Transmit Infectious Virus to Activated T Cells

doi:10.1084/jem.192.5.637

Published online 28 August 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 Moir^a, Angela Malaspina^a, Yuexia Li^b, Tae-Wook Chun^a, Tomeka Lowe^a, Joseph Adelsberger^c, Michael Baseler^c, Linda A. Ehler^a, Shuying Liu^a, Richard T. Davey, Jr.^a, Jo Ann M. Mican^a, and Anthony S. Fauci^a
^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

Correspondence to: Susan Moir, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg. 10, Rm. 6A02, Bethesda, MD 20892. Tel:301-402-4559 Fax:301-402-4122 E-mail:smoir{at}niaid.nih.gov.

The impact of HIV-associated immunopathogenesis on B cells hasbeen largely associated with indirect consequences of viralreplication. This study demonstrates that HIV interacts directlywith B cells in both lymphoid tissues and peripheral blood.B cells isolated from lymph node and peripheral blood mononuclearcells (PBMCs) of 4 and 23 chronically infected patients, respectively,demonstrated similar capacities to pass virus to activated HIV-negativePBMCs when compared with CD4⁺ cells from the same patients.However, in contrast to T cells, virus associated with B cellswas surface bound, as shown by its sensitivity to pronase andthe staining pattern revealed by in situ amplification of HIV-1RNA. Cell sorting and ligand displacing approaches establishedthat CD21 was the HIV-binding receptor on B cells, and thatthis association was mediated through complement-opsonized virus.These B cells were also found to express significantly lowerlevels of CD21 compared with HIV-negative individuals, suggestinga direct perturbing effect of HIV on B cells. These findingssuggest that B cells, although they themselves are not readilyinfected by HIV, are similar to follicular dendritic cells intheir capacity to serve as extracellular reservoirs for HIV-1.Furthermore, B cells possess the added capability of circulatingin peripheral blood and migrating through tissues where theycan potentially interact with and pass virus to T cells.

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

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