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

P. Marcatili; F. Ghiotto; C. Tenca; A. Chailyan; A. N. Mazzarello; X.-J. Yan; M. Colombo; E. Albesiano; D. Bagnara; G. Cutrona; F. Morabito; S. Bruno; M. Ferrarini; N. Chiorazzi; A. Tramontano; F. Fais

doi:10.4049/jimmunol.1300321

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

P. Marcatili, F. Ghiotto, C. Tenca, A. Chailyan, A. N. Mazzarello, X.-J. Yan, M. Colombo, E. Albesiano, D. Bagnara, G. Cutrona, F. Morabito, S. Bruno, M. Ferrarini, N. Chiorazzi, A. Tramontano, F. Fais

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20 Scopus citations

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. Copyright © 2013 by The American Association of Immunologists, Inc.

Original language	English (US)
Pages (from-to)	5771-5778
Number of pages	8
Journal	The Journal of Immunology
Volume	190
Issue number	11
DOIs	https://doi.org/10.4049/jimmunol.1300321
State	Published - May 1 2013
Externally published	Yes

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledged KAUST grant number(s): KUK-I1-012-43
Acknowledgements: 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.
This publication acknowledges KAUST support, but has no KAUST affiliated authors.

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10.4049/jimmunol.1300321

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Marcatili, P., Ghiotto, F., Tenca, C., Chailyan, A., Mazzarello, A. N., Yan, X.-J., Colombo, M., Albesiano, E., Bagnara, D., Cutrona, G., Morabito, F., Bruno, S., Ferrarini, M., Chiorazzi, N., Tramontano, A., & Fais, F. (2013). Igs Expressed by Chronic Lymphocytic Leukemia B Cells Show Limited Binding-Site Structure Variability. The Journal of Immunology, 190(11), 5771-5778. https://doi.org/10.4049/jimmunol.1300321

@article{450bfc2739a04961ab3c51567d658411,

title = "Igs Expressed by Chronic Lymphocytic Leukemia B Cells Show Limited Binding-Site Structure Variability",

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. Copyright {\textcopyright} 2013 by The American Association of Immunologists, Inc.",

author = "P. Marcatili and F. Ghiotto and C. Tenca and A. Chailyan and Mazzarello, {A. N.} and X.-J. Yan and M. Colombo and E. Albesiano and D. Bagnara and G. Cutrona and F. Morabito and S. Bruno and M. Ferrarini and N. Chiorazzi and A. Tramontano and F. Fais",

note = "KAUST Repository Item: Exported on 2020-10-01 Acknowledged KAUST grant number(s): KUK-I1-012-43 Acknowledgements: 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. This publication acknowledges KAUST support, but has no KAUST affiliated authors.",

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month = may,

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doi = "10.4049/jimmunol.1300321",

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Marcatili, P, Ghiotto, F, Tenca, C, Chailyan, A, Mazzarello, AN, Yan, X-J, Colombo, M, Albesiano, E, Bagnara, D, Cutrona, G, Morabito, F, Bruno, S, Ferrarini, M, Chiorazzi, N, Tramontano, A & Fais, F 2013, 'Igs Expressed by Chronic Lymphocytic Leukemia B Cells Show Limited Binding-Site Structure Variability', The Journal of Immunology, vol. 190, no. 11, pp. 5771-5778. https://doi.org/10.4049/jimmunol.1300321

TY - JOUR

T1 - Igs Expressed by Chronic Lymphocytic Leukemia B Cells Show Limited Binding-Site Structure Variability

AU - Marcatili, P.

AU - Ghiotto, F.

AU - Tenca, C.

AU - Chailyan, A.

AU - Mazzarello, A. N.

AU - Yan, X.-J.

AU - Colombo, M.

AU - Albesiano, E.

AU - Bagnara, D.

AU - Cutrona, G.

AU - Morabito, F.

AU - Bruno, S.

AU - Ferrarini, M.

AU - Chiorazzi, N.

AU - Tramontano, A.

AU - Fais, F.

N1 - KAUST Repository Item: Exported on 2020-10-01 Acknowledged KAUST grant number(s): KUK-I1-012-43 Acknowledgements: 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. This publication acknowledges KAUST support, but has no KAUST affiliated authors.

PY - 2013/5/1

Y1 - 2013/5/1

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. Copyright © 2013 by The American Association of Immunologists, Inc.

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. Copyright © 2013 by The American Association of Immunologists, Inc.

UR - http://hdl.handle.net/10754/598554

UR - http://www.jimmunol.org/lookup/doi/10.4049/jimmunol.1300321

UR - http://www.scopus.com/inward/record.url?scp=84878082007&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1300321

DO - 10.4049/jimmunol.1300321

M3 - Article

C2 - 23636053

SN - 0022-1767

VL - 190

SP - 5771

EP - 5778

JO - The Journal of Immunology

JF - The Journal of Immunology

IS - 11

ER -

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

Abstract

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