Cochaperone Mzb1 is a key effector of Blimp1 in plasma cell differentiation and beta 1-integrin function
AuthorAndreani, V; Ramamoorthy, S; Pandey, A; Lupar, E; Nutt, SL; Laemmermann, T; Grosschedl, R
Source TitleProceedings of the National Academy of Sciences of USA
PublisherNATL ACAD SCIENCES
University of Melbourne Author/sNutt, Stephen
AffiliationMedical Biology (W.E.H.I.)
Document TypeJournal Article
CitationsAndreani, V., Ramamoorthy, S., Pandey, A., Lupar, E., Nutt, S. L., Laemmermann, T. & Grosschedl, R. (2018). Cochaperone Mzb1 is a key effector of Blimp1 in plasma cell differentiation and beta 1-integrin function. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 115 (41), pp.E9630-E9639. https://doi.org/10.1073/pnas.1809739115.
Access StatusOpen Access
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.
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