Transcription factor MIST1 in terminal differentiation of mouse and human plasma cells

Benjamin J. Capoccia, Jochen K.M. Lennerz, Andrew J. Bredemeyer, Jeffery M. Klco, John L. Frater, Jason C. Mills

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Despite their divergent developmental ancestry, plasma cells and gastric zymogenic (chief) cells share a common function: highcapacity secretion of protein. Here we show that both cell lineages share increased expression of a cassette of 269 genes, most of which regulate endoplasmic reticulum (ER) and Golgi function, and they both induce expression of the transcription factors X-box binding protein 1 (Xbp1) and Mist1 during terminal differentiation. XBP1 is known to augment plasma cell function by establishing rough ER, and MIST1 regulates secretory vesicle trafficking in zymogenic cells. We examined morphology and function of plasma cells in wild-type and Mist1-/- mice and found subtle differences in ER structure but no overall defect in plasma cell function, suggesting that Mist1 may function redundantly in plasma cells. We next reasoned that MIST1 might be useful as a novel and reliable marker of plasma cells. We found that MIST1 specifically labeled normal plasma cells in mouse and human tissues, and, moreover, its expression was also characteristic of plasma cell differentiation in a cohort of 12 human plasma cell neoplasms. Overall, our results show that MIST1 is enriched upon plasma cell differentiation as a part of a genetic program facilitating secretory cell function and also that MIST1 is a novel marker of normal and neoplastic plasma cells in mouse and human tissues.

Original languageEnglish
Pages (from-to)174-186
Number of pages13
JournalPhysiological genomics
Volume43
Issue number3
DOIs
StatePublished - Feb 2011

Keywords

  • Plasma cell neoplasm

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