HUMAN MOUSE RADIATION CHIMERA GENERATED FROM PBMC OF B-CHRONIC LYMPHOCYTIC-LEUKEMIA PATIENTS WITH AUTOIMMUNE HEMOLYTIC-ANEMIA PRODUCE ANTI-HUMAN RED-CELL ANTIBODIES/

Previous studies performed in our laboratory have shown that B-CLL cel ls are involved in the production of anti-red cell autoantibodies, pro viding a possible mechanism for the autoimmune hemolytic anemia occurr ing during the course of B-CLL. In order to confirm this hypothesis, w e attempted to transfer human B-CLL with AIHA to immunodeficient mice. Peripheral blood mononuclear cells (PBMC) from 11 B-CLL patients suff ering from AIHA were transplanted into the peritoneal cavity of lethal ly irradiated Balb/c mice reconstituted with SCID bone marrow. Chimeri c mice generated from PBMC of these patients (in stage III-IV of the d isease) exhibited an engraftment profile with dominance of tumor cells and minuscule levels of T cells. Eighty-five percent of the chimeric mice generated from 10 out of the 11 B-CLL patients with Coombs'-posit ive AIHA, produced human Ig with anti-human red cell specificity as de tected by indirect anti-globulin test. In addition, anti-red cell auto -antibodies were produced in 36% of chimeric mice generated from PBMC of Coombs'-negative B-CLL. In contrast, control experiments in which s plenic cells from idiopathic AIHA or PBMC from normal donors were tran splanted, failed to produce anti-RBC. This in vivo model further suppo rts the relationship between the B cell expansion and the autoimmune h emolytic process.