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. Copyright © 2006 John Wiley & Sons, Ltd.