Cochaperone Mzb1 is a key effector of Blimp1 in plasma cell differentiation and β1-integrin function

Proc Natl Acad Sci U S A. 2018 Oct 9;115(41):E9630-E9639. doi: 10.1073/pnas.1809739115. Epub 2018 Sep 26.

Abstract

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 show a reduced activation of β1-integrin, which contributes to the impaired plasmablast differentiation and migration of antibody-secreting cells to the bone marrow. Thus, Mzb1 function is required for multiple aspects of plasma cell differentiation.

Keywords: Blimp1; Grp94; Mzb1; integrin; plasma cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism*
  • Cell Differentiation / physiology*
  • Immunoglobulin M / genetics
  • Immunoglobulin M / metabolism
  • Integrin beta1 / genetics
  • Integrin beta1 / metabolism*
  • Mice
  • Mice, Knockout
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Plasma Cells / cytology
  • Plasma Cells / metabolism*
  • Positive Regulatory Domain I-Binding Factor 1 / genetics
  • Positive Regulatory Domain I-Binding Factor 1 / metabolism*

Substances

  • Immunoglobulin M
  • Integrin beta1
  • Molecular Chaperones
  • Prdm1 protein, mouse
  • pERp1 protein, mouse
  • Positive Regulatory Domain I-Binding Factor 1