Mzb1 Protein Regulates Calcium Homeostasis, Antibody Secretion, and Integrin Activation in Innate-like B Cells

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2010 Nov 25

PMID 21093319

Citations 54

Authors

Henrik Flach

Marc Rosenbaum

Marlena Duchniewicz

Sola Kim

Shenyuan L Zhang

Michael D Cahalan

Gerhard Mittler

Rudolf Grosschedl

Affiliations

Soon will be listed here.

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.

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