title: Surface localization of high-mobility group nucleosome-binding protein 2 on leukemic B cells from patients with chronic lymphocytic leukemia is related to secondary autoimmune hemolytic anemia.
abstract: Chronic lymphocytic leukemia (CLL) is the main cause of autoimmune hemolytic anemia (AHA). However, the cellular basis underlying this strong association remains unclear. We previously demonstrated that leukemic B cells from patients with CLL recognize the erythrocyte protein Band 3, a prevalent autoantigen in AHA. Here we show that the major binding site of Band 3 on leukemic cells is an extrinsic protein identified as high-mobility group nucleosome binding protein 2 (HMGN2), a nucleosome-interacting factor which has not been previously reported at the cell surface. T lymphocytes do not express HMGN2 or bind Band 3. Removal of HMGN2 from the cell membrane abrogated the capacity of Band 3-pulsed CLL cells to induce CD4 + T cell proliferation. We conclude that surface HMGN2 in leukemic B cells is involved in Band 3 binding, uptake and presentation to CD4 + T lymphocytes, and as such may favor the initiation of AHA secondary to CLL.
authors.affiliation: Laboratory of Immunology, Institute of Experimental Medicine , CONICET, National Academy of Medicine, Buenos Aires , Argentina.
authors.forename: Pablo E
authors.initials: PE
authors.lastname: Morande
authors.forename: Mercedes
authors.initials: M
authors.lastname: Borge
authors.forename: Cecilia
authors.initials: C
authors.lastname: Abreu
authors.forename: Jeremías
authors.initials: J
authors.lastname: Galletti
authors.forename: Samanta R
authors.initials: SR
authors.lastname: Zanetti
authors.forename: Paula
authors.initials: P
authors.lastname: Nannini
authors.forename: Raimundo F
authors.initials: RF
authors.lastname: Bezares
authors.forename: Sergio
authors.initials: S
authors.lastname: Pantano
authors.forename: Guillermo
authors.initials: G
authors.lastname: Dighiero
authors.forename: Pablo
authors.initials: P
authors.lastname: Oppezzo
authors.forename: Romina
authors.initials: R
authors.lastname: Gamberale
authors.forename: Mirta
authors.initials: M
authors.lastname: Giordano
mesh_terms: D000368:Aged; D000744:Anemia, Hemolytic, Autoimmune / Q000209:etiology / Q000378:metabolism*; D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism*; D001665:Binding Sites; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D024242:HMGN2 Protein / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D011485:Protein Binding
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D024242:HMGN2 Protein
keywords: Autoimmune hemolytic anemia; B cells; HMGN2; band 3; chronic lymphocytic leukemia