Back

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.

2025-09-10 cell biology
10.1101/2025.09.10.675116 bioRxiv
Show 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.

Matching journals

The top 9 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.