Abstract
Plasma cells (PCs) are essential for protection from infection, and at the origin of incurable cancers. Current studies do not circumvent the limitations of removing PCs from their microenvironment and confound formation and maintenance. Also, the investigation of PC population dynamics has mostly relied on nucleotide analog incorporation that does not label quiescent cells, a property of most PCs. The main impediment is the lack of tools to perform specific genetic manipulation in vivo. Here we characterize a genetic tool (JchaincreERT2) in the mouse that permits first-ever specific genetic manipulation in PCs in vivo, across immunoglobulin isotypes. Using this tool, we found that splenic and bone marrow PC numbers remained constant over-time with the decay in genetically labeled PCs being compensated by unlabeled PCs, supporting homeostatic population turnover in these tissues. The JchaincreERT2 tool paves the way for an in-depth mechanistic understanding of PC biology and pathology in vivo, in their microenvironment.
Highlights
Antibodies produced by plasma cells (PCs) are crucial for immune protection against infection and for vaccination success (Nutt et al, 2015)
We investigated the level and specificity of the expression of genes associated with PCs (Xbp1, Jchain, Scd1, Irf4, and Prdm1) through the analysis of a publicly available RNA sequencing dataset for immune cell populations (ImmGen, [Heng et al, 2008])
Jchain had the highest level of transcript expression in PCs compared to non-PCs and was the most PC specific amongst all factors, with a forty-fold enrichment over germinal center (GC) B cells (B_GC_CB_Sp; Figure 1D)
Summary
Antibodies produced by plasma cells (PCs) are crucial for immune protection against infection and for vaccination success (Nutt et al, 2015). B cells terminally differentiate into PCs, a process initiated by the downregulation of the B cell transcription factor PAX5 (Kallies et al, 2007). This event allows the expression of multiple factors normally repressed by PAX5, including Xbp and Jchain (Castro and Flajnik, 2014; Nutt et al, 2015; Rinkenberger et al, 1996; Shaffer et al, 2004). The study of gene function in PC biology and pathology is a subject of intense investigation
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