INVESTIGADORES
GEFFNER Jorge Raul
artículos
Título:
4. Chronic lymphocytic leucemia cells bind and present the erythrocyte protein band 3: posible role as initiators of autoimmune hemolyitc anemia.
Autor/es:
GALLETTI J, CAƑONES C, MORANDE P, BORGE M, OPPEZZO P, GEFFNER J, BEZARES R, GAMBERALE R, GIORDANO M.
Revista:
JOURNAL OF IMMUNOLOGY
Editorial:
AMER ASSOC IMMUNOLOGISTS
Referencias:
Año: 2008 vol. 181 p. 3674 - 3683
ISSN:
0022-1767
Resumen:
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.