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LB4 High Frequency of Virus-Specific B Lymphocytes in Germinal Centers of SHIV-Infected Rhesus Monkeys
D. Margolin*1, E. Helmuth2, B. Bronfin1, N. de Rosa1, M. Axthelm3, X. Alvarez4, and N. Letvin1
1Beth Israel Deaconess Med. Ctr., Harvard Med. Sch., Boston, MA, USA; 2Univ. of Iowa Coll. of Med., Iowa City, USA; 3Oregon Regional Primate Res. Ctr., Oregon Hlth. Sci. Univ., Beaverton, USA; and 4New England Regional Primate Res. Ctr., Harvard Med. Sch., Southborough, MA, USA
Background: The etiology of the lymphadenopathy and follicular hyperplasia associated with HIV-1 infection has remained unclear. Increases in the B lymphocyte compartment could result from clonal expansion of virus-specific cells, or reflect non-specific B-cell activation.
Methods: The antigen specificity of B cells in lymphoid tissues of monkeys infected with SHIV-89.6 was assessed using an inverse immunohistochemical assay with biotinylated HIV-1 envelope gp120-89.6 (Env) as an antigen probe. Lymph nodes were obtained by biopsy on post-infection days (p.i.d.) 10, 21, 42 and at necropsy. Cryostat sections were prepared and stained with the biotinylated Env. The number of germinal centers (GCs) present and whether they stained with Env were tallied for each lymph node section.
Results: GCs containing envelope-specific B cells were first detected in lymph nodes in substantial numbers after p.i.d. 10. Env-binding B cells were present in 3% of GCs by p.i.d. 21, and 19% of GCs by p.i.d. 42. Env-binding GC lymphocytes were still numerous several months later.
Conclusions: A high percentage of the expanded GC B-cell population in SHIV-infected monkeys binds to HIV-1 Env. These methods underestimate the total virus-specific B-cell response because the monomeric rgp120-89.6 probe would not be expected to bind to antibodies that selectively recognize other 3-dimensional conformations of the envelope glycoprotein or to antibodies that were elicited by other viral gene products. Extrapolating from the present results to include these other B-cell specificities, we suggest that clonal expansion of virus-specific B cells can largely account for the follicular hyperplasia in AIDS virus-infected individuals.
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