Ontology type: schema:ScholarlyArticle
2018-06-28
AUTHORSLorenz Thurner, Sylvia Hartmann, Natalie Fadle, Maria Kemele, Theresa Bock, Moritz Bewarder, Evi Regitz, Frank Neumann, Anna Nimmesgern, Lutz von Müller, Christiane Pott, Yoo-Jin Kim, Rainer Maria Bohle, Mariusz Wasik, Stephen J. Schuster, Martin-Leo Hansmann, Klaus-Dieter Preuss, Michael Pfreundschuh
ABSTRACTThe predominant usage of VH4-34 and V3-21 and reports of stereotyped CDR3s suggest a shared antigenic target of B-cell receptors (BCR) from mantle cell lymphomas (MCL). To identify the target antigens of MCL–BCRs, BCRs from 21 patients and seven MCL cell lines were recombinantly expressed and used for antigen screening. The BCRs from 8/21 patients and 2/7 MCL cell lines reacted specifically with the autoantigen low-density lipoprotein receptor-related protein-associated protein 1 (LRPAP1). High-titered and light chain-restricted anti-LRPAP1 serum antibodies were found in MCL patients, but not in controls. LRPAP1 induced proliferation by BCR pathway activation, while an LRPAP1–ETA′ toxin-conjugate specifically killed MCL cells with LRPAP1-specific BCRs. Our results suggest a role of LRPAP1 in lymphomagenesis and maintenance of a considerable proportion of MCL cases by chronic autoantigenic stimulation, likely evolving from a chronic autoreactive B-cell response. Importantly, LRPAP1 can be used for a novel therapeutic approach that targets MCL with LRPAP1-reactive BCRs with high specificity. More... »
PAGES148-158
http://scigraph.springernature.com/pub.10.1038/s41375-018-0182-1
DOIhttp://dx.doi.org/10.1038/s41375-018-0182-1
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