LRPAP1 is a frequent proliferation-inducing antigen of BCRs of mantle cell lymphomas and can be used for specific therapeutic targeting View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-06-28

AUTHORS

Lorenz 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

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. More... »

PAGES

148-158

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41375-018-0182-1

DOI

http://dx.doi.org/10.1038/s41375-018-0182-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1105166123

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29955130


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17 schema:description 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.
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25 BCR pathway activation
26 CDR3s
27 MCL cases
28 MCL cell lines
29 MCL cells
30 MCL patients
31 VH4-34
32 activation
33 antibodies
34 antigen
35 antigen screening
36 antigenic targets
37 approach
38 cases
39 cell lines
40 cell lymphoma
41 cell receptor
42 cell responses
43 cells
44 considerable proportion
45 control
46 high specificity
47 induced proliferation
48 lines
49 lymphoma
50 lymphomagenesis
51 maintenance
52 mantle cell lymphoma
53 novel therapeutic approaches
54 pathway activation
55 patients
56 predominant usage
57 proliferation
58 proportion
59 protein 1
60 receptors
61 report
62 response
63 results
64 role
65 screening
66 serum antibodies
67 specific therapeutic targeting
68 specificity
69 stimulation
70 target
71 target antigen
72 targeting
73 therapeutic approaches
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