Rh autoantigen presentation to helper T cells in chronic lymphocytic leukemia by malignant B cells

Chronic lymphocytic leukemia (CLL) is frequently associated with autoimmune diseases directed against constituents of the blood, including hemolytic anemia (AIHA). We hypothesized that CLL cells predispose to hematologic autoimmunity by acting as aberrant antigen-presenting cells (APCs). Initially,...

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Bibliographic Details
Published in:Blood 2005-03, Vol.105 (5), p.2007-2015
Main Authors: Hall, Andrew M., Vickers, Mark A., McLeod, Ewan, Barker, Robert N.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Antibody Specificity
Antigen Presentation
Autoantibodies - blood
Autoantigens
Autoimmune Diseases - etiology
B-Lymphocytes - immunology
B-Lymphocytes - pathology
Biological and medical sciences
CD5 Antigens - analysis
Female
General aspects
Hematologic and hematopoietic diseases
Humans
Immunopathology
Leukemia, Lymphocytic, Chronic, B-Cell - blood
Leukemia, Lymphocytic, Chronic, B-Cell - complications
Leukemia, Lymphocytic, Chronic, B-Cell - immunology
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Male
Medical sciences
Middle Aged
Rh-Hr Blood-Group System - immunology
T-Cell Antigen Receptor Specificity - immunology
T-Lymphocytes, Helper-Inducer - immunology
T-Lymphocytes, Helper-Inducer - pathology
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Summary:Chronic lymphocytic leukemia (CLL) is frequently associated with autoimmune diseases directed against constituents of the blood, including hemolytic anemia (AIHA). We hypothesized that CLL cells predispose to hematologic autoimmunity by acting as aberrant antigen-presenting cells (APCs). Initially, it was confirmed that all studied patients with AIHA secondary to CLL harbored activated helper T (TH) cells specific for epitopes on the dominant red blood cell (RBC) autoantigens in primary AIHA, the Rh proteins. Rh-specific TH cells were also detected in a number of patients with CLL who, although they did not have AIHA, had low levels of anti-RBC antibody in their sera. Fractionation of putative APC populations from the peripheral blood of patients by negative selection showed that CD5+ CLL cells are the most effective cell type in processing and presenting purified Rh protein to autoreactive TH cells. This ability was confirmed using positively selected CD5+ CLL cells. Thus, our study provides the first evidence for malignant cells driving an autoimmune response by acting as aberrant APCs.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2003-10-3563