Identification of the atypically modified autoantigen Ars2 as the target of B-cell receptors from activated B-cell-type diffuse large B-cell lymphoma
oleh: Lorenz Thurner, Sylvia Hartmann, Moritz Bewarder, Natalie Fadle, Evi Regitz, Claudia Schormann, Natalia Quiroga, Maria Kemele, Wolfram Klapper, Andreas Rosenwald, Lorenz Trümper, Rainer Maria Bohle, Anna Nimmesgern, Christina Körbel, Matthias W. Lascke, Michael D. Menger, Stefan Barth, Boris Kubuschok, Anja Mottok, Dominic Kaddu-Mulindwa, Martin-Leo Hansmann, Viola Pöschel, Gerhard Held, Niels Murawski, Stephan Stilgenbauer, Frank Neumann, Klaus-Dieter Preuss, Michael Pfreundschuh
| Format: | Article |
|---|---|
| Diterbitkan: | Ferrata Storti Foundation 2020-07-01 |
Deskripsi
It has been suggested that B-cell receptor (BCRs) stimulation by specific antigens plays a pathogenic role in diffuse large B-cell lymphoma (DLBCL). Here, it was the aim to screen for specific reactivities of DLBCL-BCRs in the spectrum of autoantigens and antigens of infectious origin. Arsenite resistance protein 2 (Ars2) was identified as the BCR target of 3/5 ABC-type DLBCL cell lines and 2/11 primary DLBCL cases. Compared to controls, Ars2 was hypo-phosphorylated exclusively in cases and cell lines with Ars2-specific BCRs. In a validation cohort, hypo-phosphorylated Ars2 was found in 8/31 ABC-type, but only 1/20 germinal center B cell (GBC)-like type DLBCL. Incubation with Ars2 induced BCR-pathway activation and increased proliferation, while an Ars2/ETA-toxin conjugate induced killing of cell lines with Ars2-reactive BCRs. Ars2 appears to play a role in a subgroup of ABC-type DLBCLs. Moreover, transformed DLBCL lines with Ars2-reactive BCRs still show growth advantage after incubation with Ars2. These results provide knowledge about the pathogenic role of a specific antigen stimulating the BCR pathway in DLCBL.