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PMID:21093319

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Citation

Flach, H, Rosenbaum, M, Duchniewicz, M, Kim, S, Zhang, SL, Cahalan, MD, Mittler, G and Grosschedl, R (2010) Mzb1 protein regulates calcium homeostasis, antibody secretion, and integrin activation in innate-like B cells. Immunity 33:723-35

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.

Links

PubMed PMC3125521 Online version:10.1016/j.immuni.2010.11.013

Keywords

Animals; Antibodies/metabolism; B-Lymphocytes/metabolism; Calcium/metabolism; Cell Adhesion; Homeostasis; Integrins/metabolism; Lipopolysaccharides/immunology; Membrane Glycoproteins/metabolism; Mice; Mice, Transgenic; NFATC Transcription Factors/metabolism; Protein Disulfide-Isomerases/metabolism; Protein Folding; Proteins/chemistry; Proteins/genetics; Proteins/metabolism; Spleen/metabolism; T-Lymphocytes/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:ENPL

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9D8I1

F

Seeded From UniProt

complete

MOUSE:PDIA3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9D8I1

F

Seeded From UniProt

complete

MOUSE:MZB1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P27773

F

Seeded From UniProt

complete

MOUSE:MZB1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P08113

F

Seeded From UniProt

complete

MOUSE:MZB1

located_in

GO:0005788: endoplasmic reticulum lumen

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:MZB1

involved_in

GO:0033622: integrin activation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:MZB1

involved_in

GO:0030888: regulation of B cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:MZB1

involved_in

GO:0042127: regulation of cell population proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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