Critical roles of the E3 ubiquitin ligase FBW7 in B-cell response and the pathogenesis of experimental autoimmune arthritis.

Abstract

Proper regulation of B-cell function is essential for effective humoral immunity and maintenance of immune tolerance. Here, we found that FBW7 (F-box/WD40 repeat-containing protein 7) is highly expressed in germinal centre B and B1 cells, and confirmed that it has an intrinsic role in maintaining homeostasis of mature B cells and B-1 cells. FBW7 deletion led to an impairment of antibody response, and although germinal centre formation was not affected, antibody class-switch recombination and affinity maturation processes were defective. Likewise, memory immune response was severely impaired. Moreover, FBW7 ablation ameliorated the pathogenesis of an autoimmune disease model, collagen-induced arthritis, by reducing the production of anti-collagen II autoantibodies. Taken together, these data suggest that FBW7 may be an attractive target for developing new therapeutics for the treatment of autoimmune diseases.

• Authors: Chunlei Feng, Lingyun Li, Lei Zhou, Dali Li, Mingyao Liu, Shuhua Han, Biao Zheng
• Journal: Immunology (Immunology) Vol. 164 Issue 3 Pg. 617-636 (11 2021) ISSN: 1365-2567 [Electronic] England
• PMID: 34351636 (Publication Type: Journal Article)
• Copyright: © 2021 John Wiley & Sons Ltd.

Chemical References

• F-Box-WD Repeat-Containing Protein 7
• Fbxw7 protein, mouse
• Collagen

Topics

• Animals
• Arthritis, Experimental (diagnosis, immunology, pathology)
• B-Lymphocytes (immunology, metabolism)
• Collagen (administration & dosage, immunology)
• F-Box-WD Repeat-Containing Protein 7 (genetics, metabolism)
• Female
• Germinal Center (cytology, immunology, metabolism)
• Humans
• Immunoglobulin Class Switching (genetics)
• Immunologic Memory
• Male
• Mice
• Mice, Knockout
• Severity of Illness Index
• Ubiquitination (immunology)