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 prev...

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Bibliographic Details
Published in:Leukemia & lymphoma 2015-04, Vol.56 (4), p.1115-1122
Main Authors: Morande, Pablo E., Borge, Mercedes, Abreu, Cecilia, Galletti, Jeremías, Zanetti, Samanta R., Nannini, Paula, Bezares, Raimundo F., Pantano, Sergio, Dighiero, Guillermo, Oppezzo, Pablo, Gamberale, Romina, Giordano, Mirta
Format: Article
Language:English
Subjects:
Aged
Anemia, Hemolytic, Autoimmune - etiology
Anemia, Hemolytic, Autoimmune - metabolism
Anion Exchange Protein 1, Erythrocyte - metabolism
Autoimmune hemolytic anemia
B cells
B-Lymphocytes - metabolism
band 3
Binding Sites
Cell Line, Tumor
Cell Membrane - metabolism
Cells, Cultured
chronic lymphocytic leukemia
Female
Flow Cytometry
HMGN2
HMGN2 Protein - metabolism
Humans
Hydrogen-Ion Concentration
Leukemia, Lymphocytic, Chronic, B-Cell - complications
Leukemia, Lymphocytic, Chronic, B-Cell - metabolism
Male
Microscopy, Confocal
Microscopy, Fluorescence
Middle Aged
Protein Binding
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Summary: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.
ISSN:1042-8194
1029-2403
DOI:10.3109/10428194.2014.957205