Critical roles of the E3 ubiquitin ligase FBW7 in B-cell response and the pathogenesis of experimental autoimmune arthritis.
Immunology
; 164(3): 617-636, 2021 11.
Article
in En
| MEDLINE
| ID: mdl-34351636
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Arthritis, Experimental
/
B-Lymphocytes
/
F-Box-WD Repeat-Containing Protein 7
Type of study:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
Immunology
Year:
2021
Type:
Article
Affiliation country:
China