Sec22b is a critical and nonredundant regulator of plasma cell maintenance

Abstract

Despite the essential role of plasma cells in health and disease, the cellular mechanisms controlling their survival and secretory capacity are still poorly understood. Here, we identified the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) Sec22b as a unique and critical regulator of plasma cell maintenance and function. In the absence of Sec22b, plasma cells were hardly detectable and serum antibody titers were dramatically reduced. Accordingly, Sec22b -deficient mice fail to mount a protective immune response. At the mechanistic level, we demonstrated that Sec22b contributes to efficient antibody secretion and is a central regulator of plasma cell maintenance through the regulation of their transcriptional identity and of the morphology of the endoplasmic reticulum and mitochondria. Altogether, our results unveil an essential and nonredundant role for Sec22b as a regulator of plasma cell fitness and of the humoral immune response.

It takes a sec(22b) to accrue plasma cells

“…Research over the last 25 years has uncovered many of the soluble and membrane‐bound factors important for ASC differentiation and identity; however, the molecular mechanisms that facilitate ASC persistence are only now beginning to be unraveled. In a recent article, Bonaud and colleagues took the next step in this process, reporting a novel role for the protein Sec22b in regulating ASC function, organelle morphology and accumulation 1 . Using elegant techniques such as DropMap to measure single cell Ab production rates, they showed that Sec22b plays a unique and nonredundant role in ASC biology with implications for targeting of pathogenic ASCs in disease contexts (Figure 1).…”

“…As such, SNAREs are regulators of exocytosis, an important process for the secretion of high volumes of Abs, which also requires the unfolded protein response (UPR) to maintain ASC integrity 2,3 . Sec22b has been shown to be key for bidirectional transport between the ER and Golgi 1,4 . Sec22b is broadly expressed in B cells at all developmental stages but is upregulated transcriptionally and as a protein in both mouse and human ASCs 1,5 .…”

“…In a recent article, Bonaud and colleagues took the next step in this process, reporting a novel role for the protein Sec22b in regulating ASC function, organelle morphology and accumulation. 1 Using elegant techniques such as DropMap to measure single cell Ab production rates, they showed that Sec22b plays a unique and nonredundant role in ASC biology with implications for targeting of pathogenic ASCs in disease contexts (Figure 1).…”

“…2,3 Sec22b has been shown to be key for bidirectional transport between the ER and Golgi. 1,4 Sec22b is broadly expressed in B cells at all developmental stages but is upregulated transcriptionally and as a protein in both mouse and human ASCs. 1,5 Because of its more than threefold upregulation in committed ASCs in comparison to B cells, Sec22b comprises one of the key "signature" genes that defines the ASC lineage.…”

“…1,4 Sec22b is broadly expressed in B cells at all developmental stages but is upregulated transcriptionally and as a protein in both mouse and human ASCs. 1,5 Because of its more than threefold upregulation in committed ASCs in comparison to B cells, Sec22b comprises one of the key "signature" genes that defines the ASC lineage. 5 In their study, Bonaud and colleagues generated a B-cell-Sec22b knockout mouse strain (Mb1cre.Sec22b fl/fl ) to investigate the role of Sec22b in ASC biology.…”