Syndecan-1 modulates plasma cell motility and competition within the bone marrow

Abstract

Abstract Plasma cells (PC) are terminally differentiated B cells that secrete antibodies. PCs residing in the bone marrow (BM) express high levels of Syndecan-1 (Sdc1), and we have shown expression promotes PC maturation and survival in a cell intrinsic manner. Sdc1 may also mediate integrin activation and contribute to cell motility and adhesion, which may contribute to PC retention and survival. However, as PCs express heterogenous levels of Sdc1, it is unknown whether the amount of Sdc1 surface expression directly contributes to their overall fitness. Therefore, we assessed the fitness of PCs with altered Sdc1 expression within the BM. Using co-transfers of WT and Sdc1+/− donor B cells, we tracked PC responses following immunization within both WT and Sdc1+/− recipients. Donor-derived WT PCs expressed higher surface expression of Sdc1 than Sdc1+/− PCs, and WT PCs were present at higher frequencies than those derived from Sdc1+/− donors within the BM but similar within spleen. Interestingly, in Sdc1+/− recipients, there were similar frequencies of donor-derived WT and Sdc1+/− PCs suggesting reduced PC competition based on endogenous Sdc1 levels. Sdc1 has been implicated in integrin activation and potentially affects cell motility thus we assessed PC dynamics of WT, Sdc1+/−, and Sdc1−/− using intravital microscopy. PCs were motile in all hosts, but speeds were proportional to Sdc1 genotype. We screened potential ligands of Sdc1-dependent integrin activation and found that WT but not Sdc1−/− PCs bound to and moved on fibronectin. Using in vitro live cell imaging, we found binding was mediated by Sdc1 through integrin recruitment or activation. These data suggest that PC fitness is driven by Sdc1 and correlates with enhanced PC motility within the BM.