MODEL FOR HUMAN B-CHRONIC LYMPHOCYTIC-LEUKEMIA IN HUMAN MOUSE RADIATION CHIMERA - EVIDENCE FOR TUMOR-MEDIATED SUPPRESSION OF ANTIBODY-PRODUCTION IN LOW-STAGE DISEASE/

B-chronic lymphocytic leukemia (BCLL) is a lymphoproliferative disease that is characterized by clonal expansion of CD5(+) B cells. BCLL is associated with secondary immunodeficiency and hypogammaglobulinemia. It has been suggested that T-cell dysregulation may play a role in the hypogammaglobulinemia and in the increased incidence of autoimmunity in BCLL patients. We attempted to transfer human peripheral blood mono nuclear cells (PBMC) from BCLL patients in different stages of the dis ease into immunodeficient mice, PBMC from BCLL patients in stage 0, st ages I to II, and stages III to IV were transplanted into the peritone al cavity of lethally irradiated Balb/c or beige/nude/Xid (BNX) mice r adioprotected with bone marrow (BM) from severe combined immunodeficie ncy (SCID) mice. Different engraftment profiles were found in the chim eric mice 2 weeks after transplantation of PBMC according to the disea se stage of the BCLL donors, Infusion of PBMC from donors in stage led to marked engraftment of human T cells, whereas the human tumor cells could hardly be detected. In contrast, chimeric mice receiving PBMC f rom patients in stage III to IV disease exhibited engraftment with a d ominance of tumor cells, compared with a miniscule level of T cells, T he ability of the engrafted cells to produce human Ig was also found t o be correlated with the disease stage of the donor, although all dono rs had the same magnitude of hypogammaglobulinemia, Total human Ig pro duction in the chimeric mice was normal in mice receiving PBMC from do nors in stage 0, whereas in chimeric mice engrafted with PBMC from don ors in stages III to IV almost no human Igs could be detected. This di fferential reconstitution of antibody production in the mouse model ac cording to the stage of the patient's disease will allow further studi es on possible cellular interactions between malignant and immune cell s in BCLL. (C) 1997 by The American Society of Hematology.