Transinteractome analysis reveals distinct niche requirements for isotype‐based plasma cell subsets in the bone marrow

Abstract

Bone marrow (BM) long‐lived plasma cells (PCs) are essential for long‐term protection against infection, and their persistence within this organ relies on interactions with Cxcl12‐expressing stromal cells that are still not clearly identified. Here, using single cell RNAseq and in silico transinteractome analyses, we identified Leptin receptor positive (LepR+) mesenchymal cells as the stromal cell subset most likely to interact with PCs within the BM. Moreover, we demonstrated that depending on the isotype they express, PCs may use different sets of integrins and adhesion molecules to interact with these stromal cells. Altogether, our results constitute an unprecedented characterization of PC subset stromal niches and open new avenues for the specific targeting of BM PCs based on their isotype.

Plasma cell heterogeneity is driven by type of immune challenge

“…Plasma cells (PCs) are key players of the immune response through their ability to produce large quantities of antibodies (Ab). Heterogeneity within the PC compartment has previously been reported notably in terms of maturity/longevity, cytokine production and isotype usage [1][2][3][4][5][6][7] . However, the function and origin of these different subsets as well as their relevance in human lymphoid organs and in the frame of different immune challenges are not clear 1,[8][9][10] .…”