title: Mzb1 protein regulates calcium homeostasis, antibody secretion, and integrin activation in innate-like B cells.
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 T cells 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.
authors.affiliation: Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology, Stuebeweg 51, 79108 Freiburg, Germany.
authors.forename: Henrik
authors.initials: H
authors.lastname: Flach
authors.forename: Marc
authors.initials: M
authors.lastname: Rosenbaum
authors.forename: Marlena
authors.initials: M
authors.lastname: Duchniewicz
authors.forename: Sola
authors.initials: S
authors.lastname: Kim
authors.forename: Shenyuan L
authors.initials: SL
authors.lastname: Zhang
authors.forename: Michael D
authors.initials: MD
authors.lastname: Cahalan
authors.forename: Gerhard
authors.initials: G
authors.lastname: Mittler
authors.forename: Rudolf
authors.initials: R
authors.lastname: Grosschedl
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002448:Cell Adhesion; D006706:Homeostasis; D016023:Integrins / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D050778:NFATC Transcription Factors / Q000378:metabolism; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D000906:Antibodies; D016023:Integrins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D050778:NFATC Transcription Factors; D011506:Proteins; C053387:endoplasmin; C513195:Pdia3 protein, mouse; D019704:Protein Disulfide-Isomerases; D002118:Calcium