Chronic lymphocytic leukemia cells bind and present the erythrocyte protein band 3: possible role as initiators of autoimmune hemolytic anemia.
The mechanisms underlying the frequent association between chronic lymphocytic leukemia (CLL) and autoimmune hemolytic anemia are currently unclear. The erythrocyte protein band 3 (B3) is one of the most frequently targeted Ags in autoimmune hemolytic anemia. In this study, we show that CLL cells specifically recognize B3 through a still unidentified receptor. B3 interaction with CLL cells involves the recognition of its N-terminal domain and leads to its internalization. Interestingly, when binding of erythrocyte-derived vesicles as found physiologically in blood was assessed, we observed that CLL cells could only interact with inside-out vesicles, being this interaction strongly dependent on the recognition of the N-terminal portion of B3. We then examined T cell responses to B3 using circulating CLL cells as APCs. Resting B3-pulsed CLL cells were unable to induce T cell proliferation. However, when deficient costimulation was overcome by CD40 engagement, B3-pulsed CLL cells were capable of activating CD4(+) T cells in a HLA-DR-dependent fashion. Therefore, our work shows that CLL cells can specifically bind, capture, and present B3 to T cells when in an activated state, an ability that could allow the neoplastic clone to trigger the autoaggressive process against erythrocytes.
Galletti
Jeremías
J
Department of Immunology, Institute for Hematologic Research, National Academy of Medicine, Buenos Aires, Argentina.
Cañones
Cristian
C
Morande
Pablo
P
Borge
Mercedes
M
Oppezzo
Pablo
P
Geffner
Jorge
J
Bezares
Raimundo
R
Gamberale
Romina
R
Giordano
Mirta
M
D000368:Aged; D000744:Anemia, Hemolytic, Autoimmune; D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism*; D000938:Antigen-Presenting Cells; D049109:Cell Proliferation; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000473:pathology*; D008213:Lymphocyte Activation; D008875:Middle Aged; D011485:Protein Binding; D013601:T-Lymphocytes / Q000276:immunology
D001457:Anion Exchange Protein 1, Erythrocyte