The significance of spontaneously immortalized B lymphocytes from patients with AIDS-related non-Hodgkin’s lymphoma and HIV-infected individuals

Abstract

Reliable tumor biomarkers for risk assessment, screening, detection, diagnosis, and prognosis remain an unmet need for patients with AIDS-Related Non-Hodgkin’s Lymphoma (AIDS-NHL) and its high risk population–HIV/AIDS patients. In this study, we generated spontaneously immortalized B lymphocyte cell (SIBC) lines by culturing peripheral blood mononuclear cells (PBMCs) derived from AIDS-NHL and HIV/AIDS patients, then evaluated their clinical significance for detection, diagnosis, and prognosis. From 34 AIDS-NHL and 71 HIV/AIDS patients, we generated 14 AIDS-NHL-SIBC and 6 HIV-SIBC lines, respectively. Among 14 AIDS-NHL-SIBC lines, 12 SIBCs were derived from patients with poor prognoses. All SIBCs presented main markers typical of memory B-cells (CD3−CD20+CD27+) and the majority of cells expressed NHL related immunologic proteins (BCL-2, MUM-1. Ki67, etc.). AIDS-NHL-SIBCs exhibited the typical biological characteristics of tumor cells, including monoclonal Ig gene rearrangement, abnormal chromosome, and growth of xenograft tumors in NOD/SCID mice, while HIV-SIBCs possessed partial tumor cell properties, but no xenograft tumors. These findings suggest that the AIDS-NHL-SIBC lines are representative of the malignant B-lymphocytes circulating in AIDS-NHL patients (CTC), while HIV-SIBC might be a CTC precursor in HIV/AIDS patients. These data provide evidence of a potentially valuable diagnostic and prognostic biomarker for AIDS-NHL patients, and present a basis for early screening of NHL among HIV/AIDS patients.