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

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

Research output: Contribution to journalJournal articleResearchpeer-review

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.
Original languageEnglish
JournalJournal of Immunology
Volume190
Issue number11
Pages (from-to)5771-5778
ISSN0022-1767
DOIs
Publication statusPublished - 2013
Externally publishedYes

Bibliographical note

This work was supported by Associazione Italiana Ricerca sul Cancro (IG-10698 to F.F.; IG-10492 to M.F.); Compagnia di San Paolo (4824 SD/CV, 2007.2880 to F.F.); Fondazione Maria Piaggio Casarsa, Genova, Italy (to F.G.); the National Institutes of Health (Grant RO1 CA81554 to N.C.); and King Abdullah University of Science and Technology (Grant KUK-I1-012-43 to A.T.). M.C. has a fellowship from the Associazione Italiana Ricerca sul Cancro 5 per Mille

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