Distinct homotypic B-cell receptor interactions shape the outcome of chronic lymphocytic leukaemia
Citations Over TimeTop 10% of 2017 papers
Abstract
Cell-autonomous B-cell receptor (BcR)-mediated signalling is a hallmark feature of the neoplastic B lymphocytes in chronic lymphocytic leukaemia (CLL). Here we elucidate the structural basis of autonomous activation of CLL B cells, showing that BcR immunoglobulins initiate intracellular signalling through homotypic interactions between epitopes that are specific for each subgroup of patients with homogeneous clinicobiological profiles. The molecular details of the BcR-BcR interactions apparently dictate the clinical course of disease, with stronger affinities and longer half-lives in indolent cases, and weaker, short-lived contacts mediating the aggressive ones. The diversity of homotypic BcR contacts leading to cell-autonomous signalling reconciles the existence of a shared pathogenic mechanism with the biological and clinical heterogeneity of CLL and offers opportunities for innovative treatment strategies.
Related Papers
- → B cell receptor signal strength determines B cell fate(2004)555 cited
- → Biochemistry of Antigen Receptor Signaling in Mature and Developing B Lymphocytes(1997)30 cited
- → The effect of B cell receptor affinity on lipid mediated B cell receptor antigen microclustering (109.1)(2011)
- Chronic Lymphocytic Leukemia: The B cell receptor and beyond(2020)
- The actin cytoskeleton coordinates the signal transduction and antigen processing functions of the B cell antigen receptor(2013)