Mir-17-92 regulates bone marrow homing of plasma cells and production of immunoglobulin G2c

Shengli Xu; Xijun Ou; Jianxin Huo; Kristen Lim; Yuhan Huang; Sheena Chee; Kong-Peng Lam

doi:10.1038/ncomms7764

Mir-17-92 regulates bone marrow homing of plasma cells and production of immunoglobulin G2c

Nat Commun. 2015 Apr 17:6:6764. doi: 10.1038/ncomms7764.

Authors

Shengli Xu¹, Xijun Ou², Jianxin Huo², Kristen Lim², Yuhan Huang², Sheena Chee², Kong-Peng Lam³

Affiliations

¹ 1] Bioprocessing Technology Institute, Agency for Science, Technology and Research (A-STAR), Singapore 138668 [2] Department of Physiology, National University of Singapore, Singapore, Singapore 117597.
² Bioprocessing Technology Institute, Agency for Science, Technology and Research (A-STAR), Singapore 138668.
³ 1] Bioprocessing Technology Institute, Agency for Science, Technology and Research (A-STAR), Singapore 138668 [2] Department of Physiology, National University of Singapore, Singapore, Singapore 117597 [3] Department of Microbiology, National University of Singapore, Singapore 117545.

PMID: 25881561
DOI: 10.1038/ncomms7764

Abstract

The polycistronic mir-17-92 cluster, also known as oncomir-1, was previously shown to be essential for early B lymphopoiesis. However, its role in late-stage B-cell differentiation and function remains unexplored. Here we ablate mir-17-92 in mature B cells and demonstrate that mir-17-92 is dispensable for conventional B-cell development in the periphery. Interestingly, mir-17-92-deficiency in B cells leads to enhanced homing of plasma cells to the bone marrow during T-cell-dependent immune response and selectively impairs IgG2c production. Mechanistically, mir-17-92 directly represses the expression of Sphingosine 1-phosphate receptor 1 and transcription factor IKAROS, which are, respectively, important for plasma cell homing and IgG2c production. We further show that deletion of mir-17-92 could reduce IgG2c anti-DNA autoantibody production and hence mitigate immune complex glomerulonephritis in Shp1-deficient mice prone to autoimmunity. Our results identify important roles for mir-17-92 in the regulation of peripheral B-cell function.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Antinuclear / biosynthesis
B-Lymphocytes / immunology*
Bone Marrow / immunology
Cell Differentiation / genetics
Cell Differentiation / immunology
Cell Movement / genetics*
Cell Movement / immunology
Flow Cytometry
Glomerulonephritis / genetics
Glomerulonephritis / immunology
Ikaros Transcription Factor / genetics
Ikaros Transcription Factor / metabolism
Immune Complex Diseases / genetics
Immune Complex Diseases / immunology
Immunoglobulin G / biosynthesis*
Mice
MicroRNAs / genetics*
MicroRNAs / immunology
Plasma Cells / immunology*
Protein Tyrosine Phosphatase, Non-Receptor Type 6 / genetics
Receptors, Lysosphingolipid / genetics
Receptors, Lysosphingolipid / metabolism
Sphingosine-1-Phosphate Receptors
T-Lymphocytes / immunology

Substances

Antibodies, Antinuclear
Immunoglobulin G
MIRN17-92 microRNA, mouse
MicroRNAs
Receptors, Lysosphingolipid
S1pr1 protein, mouse
Sphingosine-1-Phosphate Receptors
Zfpn1a1 protein, mouse
Ikaros Transcription Factor
Protein Tyrosine Phosphatase, Non-Receptor Type 6
Ptpn6 protein, mouse