Fig 7. Model for LTβR over-expression (OE) effect on PC accumulation.

In WT PCs, TACI and BCMA are highly expressed while LTβR expression is very low. Under conditions where LTβR is OE, there is an overall increase in signaling via NF-kB leading to augmented Bcl2-family protein expression and reduced apoptosis, and to increases in other NF-kB target genes that augment PC accumulation. While TACI and BCMA signaling is ligand (BAFF, APRIL) dependent, the OE LTβR may signal in a ligand independent manner. Chronic LTβR OE in PCs due to gene amplification may allow marked over accumulation of PCs, increasing the chances of additional genetic variants emerging and progression to MM.