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    Cochaperone Mzb1 is a key effector of Blimp1 in plasma cell differentiation and beta 1-integrin function

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    Author
    Andreani, V; Ramamoorthy, S; Pandey, A; Lupar, E; Nutt, SL; Laemmermann, T; Grosschedl, R
    Date
    2018-10-09
    Source Title
    Proceedings of the National Academy of Sciences of USA
    Publisher
    NATL ACAD SCIENCES
    University of Melbourne Author/s
    Nutt, Stephen
    Affiliation
    Medical Biology (W.E.H.I.)
    Metadata
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    Document Type
    Journal Article
    Citations
    Andreani, 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 Status
    Open Access
    URI
    http://hdl.handle.net/11343/253226
    DOI
    10.1073/pnas.1809739115
    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.

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