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Journal of Virology, April 2002, p. 3965-3973, Vol. 76, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.8.3965-3973.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

High Frequency of Virus-Specific B Lymphocytes in Germinal Centers of Simian-Human Immunodeficiency Virus-Infected Rhesus Monkeys

David H. Margolin,1* Erika F. Helmuth Saunders,1,{dagger} Benjamin Bronfin,1 Nicole de Rosa,1 Michael K. Axthelm,2 Xavier Alvarez,3,{ddagger} and Norman L. Letvin1

Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts,1 Oregon Regional Primate Research Center, Oregon Health Sciences University, Beaverton, Oregon,2 New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts3

Received 13 November 2001/ Accepted 10 January 2002

The etiology of the lymphadenopathy and follicular hyperplasia associated with human immunodeficiency virus type 1 (HIV-1) infection has remained unclear. To determine whether the B-lymphocyte expansions characteristic of this syndrome represent polyclonal and virus-specific processes, the antigen specificity of B cells in lymphoid tissues of monkeys infected with simian-human immunodeficiency virus (SHIV) chimeras was assessed using an inverse immunohistochemical assay with biotinylated HIV-1 envelope gp120 (Env) as an antigen probe. Env-binding B cells were found aggregated in lymph node and splenic germinal centers (GCs). Most Env-binding GCs also contained an unstained population of B cells, suggesting the GCs were formed by a polyclonal (oligoclonal) process. By day 42 following infection, Env-binding B cells were present in 19% of all lymph node GCs. Env-binding cells were present in 25% of GCs even during chronic infection. This extraordinarily high frequency of Env-specific B lymphocytes suggests that the expansion of virus-specific B cells may largely account for the follicular hyperplasia in AIDS virus-infected individuals.

* Corresponding author. Mailing address: Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Research East—113, 330 Brookline Ave., Boston, MA 02215. Phone: (617) 667-2394. Fax: (617) 667-8210. E-mail: david_margolin{at}caregroup.harvard.edu.

{dagger} Present address: University of Michigan Hospital, Ann Arbor, Mich.

{ddagger} Present address: Tulane Regional Primate Research Center, Tulane University Health Sciences Center, Covington, La.

Journal of Virology, April 2002, p. 3965-3973, Vol. 76, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.8.3965-3973.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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