Abstract

B-cell activating factor belonging to the tumor necrosis factor family (BAFF) and a proliferating inducing ligand (APRIL) might play an important role in the pathogenesis of systemic B-cell malignancies. However, the BAFF/APRIL system has not been systematically evaluated in primary central nervous system lymphoma (PCNSL) to date. We assessed the expression of BAFF, APRIL and its receptors BAFF-R (BAFF receptor), BCMA (B-cell maturation antigen) and TACI (transmembrane activator and calcium modulator cyclophilin ligand interactor) in five PCNSL specimens by immunohistochemical staining. We found extensive expression of BAFF and weak to moderate expression of APRIL, BAFF-R, BCMA, and TACI in all specimens. CD20 positive cells showed expression of both ligands and receptors at the same time. Our results indicate that autocrine stimulation of the BAFF/APRIL system might be involved in the pathogenesis of PCNSL.

Highlights

  • We found r extensive expression of BAFF and weak to e moderate expression of a proly liferating inducing ligand (APRIL), BAFF-R, BCMA, and TACI in all specimens

  • BAFF/APRIL signaling pathway has been shown in various systemic lymphomas.[4,5,6,7,8]

  • Overexpression of APRIL has been correlated kappa-B (NF-kB)-regulated genes has been We evaluated tissue sections from five with higher aggressiveness of B-cell lymdetected suggesting that this signaling path- patients with newly-diagnosed primary central nervous system e lymphoma (PCNSL)

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Summary

Materials and Methods

We assessed the s expression of BAFF, APRIL and its receptors u BAFF-R (BAFF receptor), BCMA (B-cell maturation antigen) and TACI (transmembrane l activator and calcium modulator cyclophilin ia ligand interactor) in five PCNSL specimens by c immunohistochemical staining. We used the following primary antibodies: rabbit antihuman BAFF (ab117256, dilution 1:12.5), goat anti-human APRIL (ab110848, dilution 1:100), rabbit anti-human BAFF-R (ab5965, dilution 1:100), rabbit anti-human BCMA (ab115315, dilution 1:50), rabbit anti-human TACI (ab79023, dilution 1:50), mouse anti-human CD20 [ab9475 (L26), dilution 1:35], rabbit antihuman CD3 (ab5690, dilution 1:100) (all ABCAM, Cambridge, MA, USA), mouse antihuman CD68 (PG-M1, M 0876, dilution 1:100, Dako, Glostrup, Denmark) and rabbit antihuman BAFF (ABIN740175, dilution 1:50, antibodies-online inc., Atlanta, GA, USA). Two tumors showed extensive expression of TACI and weak to moderate expression of BCMA and BAFF-R. As for the ligands, expression of BAFF-R, BCMA and TACI was found mainly within CD20 positive cells. New Expression of components of the treatment targets are urgently needed

Little is known about the pathogenesis of Results
Findings
These results indicate a pathogenic role of the
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