TY - JOUR
T1 - Igs expressed by chronic lymphocytic leukemia B cells show limited binding-site structure variability
AU - Marcatili, Paolo
AU - Ghiotto, Fabio
AU - Tenca, Claudya
AU - Chailyan, Anna
AU - Mazzarello, Andrea N.
AU - Yan, Xiao Jie
AU - Colombo, Monica
AU - Albesiano, Emilia
AU - Bagnara, Davide
AU - Cutrona, Giovanna
AU - Morabito, Fortunato
AU - Bruno, Silvia
AU - Ferrarini, Manlio
AU - Chiorazzi, Nicholas
AU - Tramontano, Anna
AU - Fais, Franco
PY - 2013/6/1
Y1 - 2013/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84878082007&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878082007&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1300321
DO - 10.4049/jimmunol.1300321
M3 - Article
C2 - 23636053
AN - SCOPUS:84878082007
VL - 190
SP - 5771
EP - 5778
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 11
ER -