Cochaperone Mzb1 is a key effector of Blimp1 in plasma cell differentiation and β1-integrin function
- Author(s)
- Andreani, V; Ramamoorthy, S; Pandey, A; Lupar, E; Nutt, SL; Lammermann, T; Grosschedl, R;
- Details
- Publication Year 2018-09-26,Volume 115,Issue #41,Page E9630-E9639
- Journal Title
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type
- Journal Article
- 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 beta1-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.
- Publisher
- NAS
- Research Division(s)
- Molecular Immunology
- PubMed ID
- 30257949
- Publisher's Version
- https://doi.org/10.1073/pnas.1809739115
- Open Access at Publisher's Site
https://doi.org/10.1073/pnas.1809739115- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2018-10-11 04:23:12
Last Modified: 2018-10-12 12:07:44