TY - JOUR
T1 - Chronic lymphocytic leukemia cells bind and present the erythrocyte protein band 3
T2 - Possible role as initiators of autoimmune hemolytic anemia
AU - Galletti, Jeremías
AU - Cañones, Cristian
AU - Morande, Pablo
AU - Borge, Mercedes
AU - Oppezzo, Pablo
AU - Geffner, Jorge
AU - Bezares, Raimundo
AU - Gamberale, Romina
AU - Giordano, Mirta
PY - 2008/9/1
Y1 - 2008/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=51549116936&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.181.5.3674
DO - 10.4049/jimmunol.181.5.3674
M3 - Article
C2 - 18714043
AN - SCOPUS:51549116936
SN - 0022-1767
VL - 181
SP - 3674
EP - 3683
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -