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bioRxiv · 10.1101/2025.09.10.675116

BCMA signaling from the Golgi apparatus in B cells

manfroi, b.·chemkhi, z.·baert, l.·kakunuri, t.·micheau, o.·govers, r.·wajant, h.·Schneider, P.·sturm, n.·huard, b.
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Abstract

B-cell maturation antigen (BCMA) targeting gained a rapid approval for multiple myeloma, and is currently investigated in B-cell lymphomas. Here, we report that the trans Golgi network (TGN) retained BCMA due to a motif in its transmembrane/cytoplasmic domain in diffuse large B-cell lymphomas (DLBCL). To achieve signaling, one of its ligands, a proliferation inducing ligand (APRIL), bound to surface heparan sulfate proteoglycans (HSPGs), got endocytosed by the calveolin pathway and trafficked to the TGN via the retrograde route. In the TGN, APRIL/BCMA interactions activated the NF-{kappa}B pathway. BCMA ubiquitination followed by proteosomal degradation mediated signal termination. Growth impairment of DLBCL xenografts in APRIL-deficient animals confirmed the in vivo activity of TGN BCMA. Our study constitutes the first description for a signal activity from the Golgi apparatus among the TNF receptor family.

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manfroi, b., chemkhi, z., baert, l., kakunuri, t., micheau, o., govers, r., wajant, h., Schneider, P., sturm, n., huard, b.. 2025-09-10. BCMA signaling from the Golgi apparatus in B cells. https://doi.org/10.1101/2025.09.10.675116

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