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Igs Expressed by Chronic Lymphocytic Leukemia B Cells Show Limited Binding-Site Structure Variability

2013; American Association of Immunologists; Volume: 190; Issue: 11 Linguagem: Inglês

10.4049/jimmunol.1300321

1550-6606

Paolo Marcatili, Fabio Ghiotto, Claudya Tenca, Anna Chailyan, Andrea Nicola Mazzarello, Xiao‐Jie Yan, Monica Colombo, Emilia Albesiano, Davide Bagnara, Giovanna Cutrona, Fortunato Morabito, Silvia Bruno, Manlio Ferrarini, Nicholas Chiorazzi, Anna Tramontano, Franco Fais,

Immunodeficiency and Autoimmune Disorders

Abstract Ag selection has been suggested to play a role in chronic lymphocytic leukemia (CLL) pathogenesis, but no large-scale analysis has been performed so far on the structure of the Ag-binding sites (ABSs) of leukemic cell Igs. We sequenced both H and L chain V(D)J rearrangements from 366 CLL patients and modeled their three-dimensional structures. The resulting ABS structures were clustered into a small number of discrete sets, each containing ABSs with similar shapes and physicochemical properties. This structural classification correlates well with other known prognostic factors such as Ig mutation status and recurrent (stereotyped) receptors, but it shows a better prognostic value, at least in the case of one structural cluster for which clinical data were available. These findings suggest, for the first time, to our knowledge, on the basis of a structural analysis of the Ab-binding sites, that selection by a finite quota of antigenic structures operates on most CLL cases, whether mutated or unmutated.