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Chronic lymphocytic leukaemia is driven by antigen-independent cell-autonomous signalling.
- Source :
- Nature; 9/13/2012, Vol. 489 Issue 7415, p309-312, 4p, 4 Graphs
- Publication Year :
- 2012
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00280836
- Volume :
- 489
- Issue :
- 7415
- Database :
- Complementary Index
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 79961135
- Full Text :
- https://doi.org/10.1038/nature11309