Patients with advanced AIDS are at increased risk for developing aggressive B cell lymphomas. However, even prior to the development of significant CD4+ T cell depletion, patients infected with HIV- I may develop B lymphocyte abnormalities. Recent studies indicate that immunoglobulins (Ig) encoded by a subset of Ig heavy chain variable region genes (VH genes) of the VH3 subgroup have innate binding activity for HIV gpl20, similar to that of the CD4 surface molecule expressed by T cells and monocytes. However, the pathogenic significance of this binding activity is unclear. In addition, preliminary studies of AIDS-associated lymphomas suggest that the lg V gene repertoire expressed by such tumors is highly restricted. We propose to investigate the relationship(s) between the expression of Ig V genes and lymphoproliferative disease in patients infected with HIV. In particular, we will; 1) evaluate the Ig V gene repertoire expressed by B cells in serial blood samples collected from patients infected with HIV who have or have not developed AIDS-associated lymphoproliferative disease using a novel RT-aPCR ELISA developed in our laboratory; 2) evaluate the Ig V gene repertoire expressed by polyclonal B cells in hyperplastic lymphoid tissue obtained from patients with AIDS-associated immunoproliferative disorder; 3) evaluate lg genes expressed by AIDS- associated lymphoma for lg V gene intraclonal diversity and/or Ig V gene somatic mutation; 4) examine whether the Ig VH genes expressed by polyclonal B lymphoblastoid cell populations influences B cell susceptibility for in vitro infection with HIV-I, and finally; 5) evaluate whether the lg expressed by AIDS-associated lymphomas specifically recognize HIV-encoded proteins and/or HIV- I-infected cells.
| Bessudo, A; Rassenti, L; Havlir, D et al. (1998) Aberrant and unstable expression of immunoglobulin genes in persons infected with human immunodeficiency virus. Blood 92:1317-23 |
| Bessudo, A; Cherepakhin, V; Johnson, T A et al. (1996) Favored use of immunoglobulin V(H)4 Genes in AIDS-associated B-cell lymphoma. Blood 88:252-60 |
