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J Immunol. 2016 Jun 1;196(11):4477-86. doi: 10.4049/jimmunol.1502043. Epub 2016 Apr 25.

STAT3 Signaling in B Cells Is Critical for Germinal Center Maintenance and Contributes to the Pathogenesis of Murine Models of Lupus.

Author information

1
Department of Medicine, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202; jun.yan@louisville.edu chuanlin.ding@louisville.edu.
2
Department of Rheumatology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, People's Republic of China;
3
Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40202;
4
Department of Medicine, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202;
5
Department of Medicine, Institute of Molecular Cardiology, University of Louisville, Louisville, KY 40292; and.
6
Section of Nephrology, Department of Medicine, University of Louisville, Louisville, KY 40202.
7
Department of Medicine, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202; Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40202; jun.yan@louisville.edu chuanlin.ding@louisville.edu.

Abstract

Ab maturation as well as memory B and plasma cell differentiation occur primarily in the germinal centers (GCs). Systemic lupus erythematosus (SLE) may develop as a result of enhanced GC activity. Previous studies have shown that the dysregulated STAT3 pathway is linked to lupus pathogenesis. However, the exact role of STAT3 in regulating SLE disease progression has not been fully understood. In this study, we demonstrated that STAT3 signaling in B cells is essential for GC formation and maintenance as well as Ab response. Increased cell apoptosis and downregulated Bcl-xL and Mcl-1 antiapoptotic gene expression were found in STAT3-deficient GC B cells. The follicular helper T cell response positively correlated with GC B cells and was significantly decreased in immunized B cell STAT3-deficient mice. STAT3 deficiency also led to the defect of plasma cell differentiation. Furthermore, STAT3 deficiency in autoreactive B cells resulted in decreased autoantibody production. Results obtained from B cell STAT3-deficient B6.MRL/lpr mice suggest that STAT3 signaling significantly contributes to SLE pathogenesis by regulation of GC reactivity, autoantibody production, and kidney pathology. Our findings provide new insights into the role of STAT3 signaling in the maintenance of GC formation and GC B cell differentiation and identify STAT3 as a novel target for treatment of SLE.

PMID:
27183592
PMCID:
PMC4875824
DOI:
10.4049/jimmunol.1502043
[Indexed for MEDLINE]
Free PMC Article

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