Mzb1 protein regulates calcium homeostasis, antibody secretion, and integrin activation in innate-like B cells. Academic Article uri icon

abstract

  • Marginal zone (MZ) B cells of the spleen and B1 cells, termed innate-like B cells, differ from follicular B cells by their attenuated Ca(2+) mobilization, fast antibody secretion, and increased cell adhesion. We identified and characterized Mzb1 as an endoplasmic reticulum-localized and B cell-specific protein that was most abundantly expressed in MZ B and B1 cells. Knockdown of Mzb1 in MZ B cells increased Ca(2+) mobilization and nuclear NFAT transcription factor localization, but reduced lipopolysaccharide-induced antibody secretion and integrin-mediated cell adhesion. Conversely, ectopic expression of an Lck-Mzb1 transgene in peripheral Tcells resulted in attenuated Ca(2+) mobilization and augmented integrin-mediated cell adhesion. In addition to its interaction with the substrate-specific chaperone Grp94, Mzb1 augmented the function of the oxidoreductase ERp57 in favoring the expression of integrins in their activated conformation. Thus, Mzb1 helps to diversify peripheral B cell functions by regulating Ca(2+) stores, antibody secretion, and integrin activation.

published proceedings

  • Immunity

altmetric score

  • 6

author list (cited authors)

  • Flach, H., Rosenbaum, M., Duchniewicz, M., Kim, S., Zhang, S. L., Cahalan, M. D., Mittler, G., & Grosschedl, R.

citation count

  • 67

complete list of authors

  • Flach, Henrik||Rosenbaum, Marc||Duchniewicz, Marlena||Kim, Sola||Zhang, Shenyuan L||Cahalan, Michael D||Mittler, Gerhard||Grosschedl, Rudolf

publication date

  • January 2010