Analysis of immunoglobulin heavy and light chain variable genes in post-transplant lymphoproliferative disorders.

Abstract

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.

• Authors: Daniela Capello, Michaela Cerri, Giuliana Muti, Marco Lucioni, Pierluigi Oreste, Annunziata Gloghini, Eva Berra, Clara Deambrogi, Silvia Franceschetti, Davide Rossi, Oscar Alabiso, Enrica Morra, Alessandro Rambaldi, Antonino Carbone, Marco Paulli, Gianluca Gaidano
• Journal: Hematological oncology (Hematol Oncol) Vol. 24 Issue 4 Pg. 212-9 (Dec 2006) ISSN: 0278-0232 [Print] England
• PMID: 16897790 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunoglobulin G
• Immunoglobulin Heavy Chains
• Immunoglobulin Light Chains
• Immunoglobulin Variable Region
• BCR protein, human
• Proto-Oncogene Proteins c-bcr

Topics

• Apoptosis (genetics)
• Burkitt Lymphoma (genetics, metabolism, pathology)
• Female
• Gene Expression Regulation, Leukemic
• Gene Rearrangement, B-Lymphocyte, Heavy Chain (genetics)
• Gene Rearrangement, B-Lymphocyte, Light Chain (genetics)
• Germinal Center (metabolism, pathology)
• Humans
• Immunoglobulin G (biosynthesis, genetics)
• Immunoglobulin Heavy Chains (genetics)
• Immunoglobulin Light Chains (biosynthesis, genetics)
• Immunoglobulin Variable Region (biosynthesis, genetics)
• Immunohistochemistry
• Male
• Mutation
• Neoplasms, Second Primary (genetics)
• Organ Transplantation
• Proto-Oncogene Proteins c-bcr (biosynthesis, genetics)
• Somatic Hypermutation, Immunoglobulin (genetics)