Chronic lymphocytic leukemia cells bind and present the erythrocyte protein band 3: Possible role as initiators of autoimmune hemolytic anemia

Jeremías Galletti, Cristian Cañones, Pablo Morande, Mercedes Borge, Pablo Oppezzo, Jorge Geffner, Raimundo Bezares, Romina Gamberale, Mirta Giordano*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

31 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3674-3683
Number of pages10
JournalJournal of Immunology
Volume181
Issue number5
DOIs
Publication statusPublished - 1 Sep 2008
Externally publishedYes

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