Abstract：
:The 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.
journal_name
Leukemiajournal_title
Leukemiaauthors
Thurner L,Hartmann S,Fadle N,Kemele M,Bock T,Bewarder M,Regitz E,Neumann F,Nimmesgern A,von Müller L,Pott C,Kim YJ,Bohle RM,Wasik M,Schuster SJ,Hansmann ML,Preuss KD,Pfreundschuh Mdoi
10.1038/s41375-018-0182-1subject
Has Abstractpub_date
2019-01-01 00:00:00pages
148-158issue
1eissn
0887-6924issn
1476-5551pii
10.1038/s41375-018-0182-1journal_volume
33pub_type
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