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 cells are involved in the production of anti-red cell autoantibodies, providing a possible mechanism for the autoimmune hemolytic anemia occurring during the course of B-CLL. In order to confirm this hypothesis, we attempted to transfer human B-CLL with AIHA to immunodeficient mice. Peripheral blood mononuclear cells (PBMC) from 11 B-CLL patients suffering from AIHA were transplanted into the peritoneal cavity of lethally irradiated Balb/c mice reconstituted with SCID bone marrow. Chimeric mice generated from PBMC of these patients (in stage III-IV of the disease) 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'-positive AIHA, produced human Ig with anti-human red cell specificity-as detected 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 splenic cells from idiopathic AIHA or PBMC from normal donors were transplanted, failed to produce anti-RBC. This in vivo model further supports the relationship between the B cell expansion and the autoimmune hemolytic process.