Immune Dysfunction and AIDS - Associated B Cell Lymphoma Non-Hodgkin's B cell lymphoma is seen in greatly-elevated frequency in HIV infection. The high frequency of B cell lymphoma seen in HIV infection may result, in part, from chronic B cell stimulation. Also, loss of immunoregulatory control of Epstein-Barr virus (EBV) infected/activated B cells may contribute to AIDS-related lymphoma (ARL). In this proposal, studies are presented to delineate immune system changes in HIV infection relevant to the development of ARL. Preliminary studies indicate that people who have advanced HIV disease show marked phenotypic changes in circulating B cells, with some cells displaying markers that are typically seen on germinal center (GC) B cells and follicular helper T cells (TFH)- Other preliminary studies show that elevated levels of B cell-stimulatory molecules precede ARL diagnosis by several years. Additionally, molecules expressed in GC B cells are seen to be induced by exposure to EBV or HIV, and are expressed in ARL cell lines. Studies described in this proposal will determine if these aberrant B cells have a phenotype that is consistent with them being GC B cell-like cells, and if these cells are seen in elevated numbers preceding ARL diagnosis. Additionally, we will determine if elevated levels of aberrant TFH-like cells are seen in HIV infection. More specifically, the aims are to: 1) characterize the phenotypically-aberrant B cells seen in HIV+ subjects, and define the immune system changes that accompany these cells, 2) determine if the phenotypically-abnormal peripheral blood B cells seen in HIV+ subjects contain cells that are potential precursors of ARL, and 3) define the expression of these aberrant B cells preceding the development of ARL. The accomplishment of these aims will provide valuable information on HIV-induced immune dysfunction and the development of ARL.