TY - JOUR
T1 - Analysis of immunoglobulin heavy and light chain variable genes in post-transplant lymphoproliferative disorders
AU - Capello, Daniela
AU - Cerri, Michaela
AU - Muti, Giuliana
AU - Lucioni, Marco
AU - Oreste, Pierluigi
AU - Gloghini, Annunziata
AU - Berra, Eva
AU - Deambrogi, Clara
AU - Franceschetti, Silvia
AU - Rossi, Davide
AU - Alabiso, Oscar
AU - Morra, Enrica
AU - Rambaldi, Alessandro
AU - Carbone, Antonino
AU - Paulli, Marco
AU - Gaidano, Gianluca
PY - 2006/12
Y1 - 2006/12
N2 - Post-transplant lymphoproliferative disorders (PTLD) derive from antigen-experienced B-cells and represent a major complication of solid organ transplantation. We characterized usage, mutation frequency and mutation pattern of immunoglobulin variable (IGV) gene rearrangements in 50 PTLD (polymorphic PTLD, n = 10; diffuse large B-cell lymphoma, n = 35; and Burkitt/Burkitt-like lymphoma, n = 5). Among PTLD yielding clonal IGV amplimers, a functional IGV heavy chain (IGHV) rearrangement was found in 40/50 (80.0%) cases, whereas a potentially functional IGV light chain rearrangement was identified in 36/46 (78.3%) PTLD. By combining IGHV and IGV light chain rearrangements, 10/50 (20.0%) PTLD carried crippling mutations, precluding expression of a functional B-cell receptor (BCR). Immunohistochemistry showed detectable expression of IG light chains in only 18/43 (41.9%) PTLD. Failure to detect a functional IGV rearrangement associated with lack of IGV expression. Our data suggest that a large fraction of PTLD arise from germinal centre (GC)-experienced B-cells that display impaired BCR. Since a functional BCR is required for normal B-cell survival during GC transit, PTLD development may implicate rescue from apoptosis and expansion of B-cells that have failed the GC reaction. The high frequency of IGV loci inactivation appears to be a peculiar feature of PTLD among immunodeficiency-associated lymphoproliferations.
AB - Post-transplant lymphoproliferative disorders (PTLD) derive from antigen-experienced B-cells and represent a major complication of solid organ transplantation. We characterized usage, mutation frequency and mutation pattern of immunoglobulin variable (IGV) gene rearrangements in 50 PTLD (polymorphic PTLD, n = 10; diffuse large B-cell lymphoma, n = 35; and Burkitt/Burkitt-like lymphoma, n = 5). Among PTLD yielding clonal IGV amplimers, a functional IGV heavy chain (IGHV) rearrangement was found in 40/50 (80.0%) cases, whereas a potentially functional IGV light chain rearrangement was identified in 36/46 (78.3%) PTLD. By combining IGHV and IGV light chain rearrangements, 10/50 (20.0%) PTLD carried crippling mutations, precluding expression of a functional B-cell receptor (BCR). Immunohistochemistry showed detectable expression of IG light chains in only 18/43 (41.9%) PTLD. Failure to detect a functional IGV rearrangement associated with lack of IGV expression. Our data suggest that a large fraction of PTLD arise from germinal centre (GC)-experienced B-cells that display impaired BCR. Since a functional BCR is required for normal B-cell survival during GC transit, PTLD development may implicate rescue from apoptosis and expansion of B-cells that have failed the GC reaction. The high frequency of IGV loci inactivation appears to be a peculiar feature of PTLD among immunodeficiency-associated lymphoproliferations.
KW - Germinal centre
KW - Immunoglobulin
KW - Lymphoma
KW - Post-transplant
KW - Somatic hypermutation
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U2 - 10.1002/hon.791
DO - 10.1002/hon.791
M3 - Article
C2 - 16897790
AN - SCOPUS:33845942227
VL - 24
SP - 212
EP - 219
JO - Hematological Oncology
JF - Hematological Oncology
SN - 0278-0232
IS - 4
ER -