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

被引：51

作者：

Andreani, Virginia ^{[1
]}

Ramamoorthy, Senthilkumar ^{[1
]}

Pandey, Abhinav ^{[1
]}

Lupar, Ekaterina ^{[1
]}

Nutt, Stephen L. ^{[2
,3
]}

Laemmermann, Tim ^{[1
]}

Grosschedl, Rudolf ^{[1
]}

机构：

[1] Max Planck Inst Immunobiol & Epigenet, Dept Cellular & Mol Immunol, D-79108 Freiburg, Germany

[2] Walter & Eliza Hall Inst Med Res, Mol Immunol Div, Parkville, Vic 3052, Australia

[3] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2018年 / 115卷 / 41期

关键词：

Mzb1; Grp94; Blimp1; integrin; plasma cell; TRANSCRIPTION FACTOR BLIMP-1; UNFOLDED PROTEIN RESPONSE; BONE-MARROW; ENDOPLASMIC-RETICULUM; ADHESION MOLECULE-1; IMMUNE-RESPONSE; INTEGRIN ACTIVATION; MONOCLONAL-ANTIBODY; MARGINAL ZONE; STROMAL CELLS;

D O I：

10.1073/pnas.1809739115

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 beta 1-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.

引用

页码：E9630 / E9639

页数：10

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