GEFFNER Jorge Raul
4. Chronic lymphocytic leucemia cells bind and present the erythrocyte protein band 3: posible role as initiators of autoimmune hemolyitc anemia.
GALLETTI J, CAÑONES C, MORANDE P, BORGE M, OPPEZZO P, GEFFNER J, BEZARES R, GAMBERALE R, GIORDANO M.
JOURNAL OF IMMUNOLOGY
AMER ASSOC IMMUNOLOGISTS
Año: 2008 vol. 181 p. 3674 - 3683
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.