title: Autoantigenic targets of B-cell receptors derived from chronic lymphocytic leukemias bind to and induce proliferation of leukemic cells.
abstract: Antigenic targets of the B-cell receptor (BCR) derived from malignant cells in chronic lymphocytic leukemia (CLL) might play a role in the pathogenesis of this neoplasm. We screened human tissue-derived protein macroarrays with antigen-binding fragments derived from 47 consecutive cases of CLL. An autoantigenic target was identified for 12/47 (25.5%) of the cases, with 3 autoantigens being the target of the BCRs from 2 patients each. Recombinantly expressed autoantigens bound specifically to the CLL cells from which the BCR used for the identification of the respective autoantigen was derived. Moreover, binding of the autoantigen to the respective leukemic cells induced a specific activation and proliferation of these cells. In conclusion, autoantigens are frequent targets of CLL-BCRs. Their specific binding to and induction of proliferation in the respective leukemic cells provide the most convincing evidence to date for the long-time hypothesized role of autoantigens in the pathogenesis of CLL.
authors.affiliation: Jose-Carreras Center for Immuno- and Gene Therapy, Department Internal Medicine I, Saarland University Medical School, Homburg (Saar), Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Zwick
authors.forename: Natalie
authors.initials: N
authors.lastname: Fadle
authors.forename: Evi
authors.initials: E
authors.lastname: Regitz
authors.forename: Maria
authors.initials: M
authors.lastname: Kemele
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.forename: Andreas
authors.initials: A
authors.lastname: Bühler
authors.forename: Michael
authors.initials: M
authors.lastname: Pfreundschuh
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Preuss
mesh_terms: D001324:Autoantigens / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*
chemical_list: D001324:Autoantigens; D019394:Ki-67 Antigen; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D011947:Receptors, Antigen, B-Cell