Cochaperone Mzb1 is a key effector of Blimp1 in plasma cell differentiation and beta 1-integrin function
Virginia Andreani, Senthilkumar Ramamoorthy, Abhinav Pandey, Ekaterina Lupar, Stephen L Nutt, Tim Laemmermann, Rudolf Grosschedl
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2018
Plasma cell differentiation involves coordinated changes in gene expression and functional properties of B cells. Here, we study the role of Mzb1, a Grp94 cochaperone that is expressed in marginal zone (MZ) B cells and during the terminal differentiation of B cells to antibody-secreting cells. By analyzing Mzb1 -/- Prdm1 +/gfp mice, we find that Mzb1 is specifically required for the differentiation and function of antibody-secreting cells in a T cell-independent immune response. We find that Mzb1-deficiency mimics, in part, the phenotype of Blimp1 deficiency, including the impaired secretion of IgM and the deregulation of Blimp1 target genes. In addition, we find that Mzb1 -/- plasmablasts s..View full abstract
We thank Eirini Trompouki for critical reading the manuscript; Marika Rott for the assistance with the manuscript preparation; Ingrid Falk and Franziska Ludin for technical assistance; members of R.G.'s department for the discussions; and the Deep Sequencing, Flow Cytometry Facility, and Mouse facilities of the Max Planck Institute. This work was supported by funds from the Max Planck Society and German Research Foundation.