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 auto-antibodies, 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.
Marcus
H
H
Immunology Dept, The Weizmann Institute of Science, Rehovot, Israel.
Shimoni
A
A
Ergas
D
D
Canaan
A
A
Dekel
B
B
Ben-David
D
D
David
M
M
Sigler
E
E
Reisner
Y
Y
Berrebi
A
A
D000368:Aged; D000369:Aged, 80 and over; D000743:Anemia, Hemolytic / Q000097:blood / Q000150:complications* / Q000276:immunology / Q000473:pathology; D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D001854:Bone Marrow Cells; D002051:Burkitt Lymphoma / Q000097:blood / Q000150:complications / Q000276:immunology* / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009367:Neoplasm Staging; D011828:Radiation Chimera; D012016:Reference Values; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014183:Transplantation, Heterologous