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Crystal structure of the BCR Fab fragment from subset #4 case CLL183Crystal structure of the BCR Fab fragment from subset #4 case CLL183
Structural highlights
Publication Abstract from PubMedCell-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. Distinct homotypic B-cell receptor interactions shape the outcome of chronic lymphocytic leukaemia.,Minici C, Gounari M, Ubelhart R, Scarfo L, Duhren-von Minden M, Schneider D, Tasdogan A, Alkhatib A, Agathangelidis A, Ntoufa S, Chiorazzi N, Jumaa H, Stamatopoulos K, Ghia P, Degano M Nat Commun. 2017 Jun 9;8:15746. doi: 10.1038/ncomms15746. PMID:28598442[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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