Chronic lymphocytic leukaemia is driven by antigen-independent cell-autonomous signalling |
| |
Authors: | Marcus Dühren-von Minden Rudolf Übelhart Dunja Schneider Thomas Wossning Martina P Bach Maike Buchner Daniel Hofmann Elena Surova Marie Follo Fabian Köhler Hedda Wardemann Katja Zirlik Hendrik Veelken Hassan Jumaa |
| |
Institution: | Centre for Biological Signaling Studies (BIOSS), Albert-Ludwigs Universit?t Freiburg, 79104 Freiburg, Germany. |
| |
Abstract: | B-cell antigen receptor (BCR) expression is an important feature of chronic lymphocytic leukaemia (CLL), one of the most prevalent B-cell neoplasias in Western countries. The presence of stereotyped and quasi-identical BCRs in different CLL patients suggests that recognition of specific antigens might drive CLL pathogenesis. Here we show that, in contrast to other B-cell neoplasias, CLL-derived BCRs induce antigen-independent cell-autonomous signalling, which is dependent on the heavy-chain complementarity-determining region (HCDR3) and an internal epitope of the BCR. Indeed, transferring the HCDR3 of a CLL-derived BCR provides autonomous signalling capacity to a non-autonomously active BCR, whereas mutations in the internal epitope abolish this capacity. Because BCR expression was required for the binding of secreted CLL-derived BCRs to target cells, and mutations in the internal epitope reduced this binding, our results indicate a new model for CLL pathogenesis, with cell-autonomous antigen-independent signalling as a crucial pathogenic mechanism. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|