BAFF Inhibition Effectively Suppresses the Development of Anti-HLA.A2 Antibody in the Highly Sensitized Mouse Model

International Journal of Molecular Sciences

Bo-Mi Kim¹  Byung Ha Chung¹  Sun Woo Lim¹  Kyoung Chan Doh¹  Chul Woo Yang¹  Eun-Jee Oh¹  Yoo-Jin Shin¹  Hyeyoung Lee²  Tae-Min Kim³  Ki Hyun Park⁴  Ji Won Min⁵ 

[1] Convergent Research Consortium for Immunologic Disease, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;Department of Laboratory Medicine, Catholic Kwandong University International St. Mary’s Hospital, Incheon 22711, Korea;Department of Medical Informatics, The Catholic University of Korea, Seoul 06591, Korea;Department of Molecular & Cell Biology, Graduate School, The Catholic University of Korea, Seoul 06591, Korea;Division of Nephrology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;

关键词: HLA.A2 transgenic mice;    sensitization;    skin allograft;    BAFF;    donor-specific antibody;   

DOI  :  10.3390/ijms22020861

来源: DOAJ

【 摘 要 】

B cell activating factor (BAFF) is a cytokine that plays a role in the survival, proliferation and differentiation of B cells. We proposed to observe the effects of BAFF inhibition on the humoral immune responses of an allosensitized mouse model using HLA.A2 transgenic mice. Wild-type C57BL/6 mice were sensitized with skin allografts from C57BL/6-Tg (HLA-A2.1)1Enge/J mice and were treated with anti-BAFF monoclonal antibody (mAb) (named Sandy-2) or control IgG1 antibody. HLA.A2-specific IgG was reduced in BAFF-inhibited mice compared to the control group (Δ-13.62 vs. Δ27.07, p < 0.05). BAFF inhibition also resulted in increased pre-pro and immature B cell proportions and decreased mature B cells in the bone marrow (p < 0.05 vs. control). In the spleen, an increase in transitional B cells was observed with a significant decrease in marginal and follicular B cells (p < 0.05 vs. control). There was no significant difference in the proportions of long-lived plasma and memory B cells. Microarray analysis showed that 19 gene probes were significantly up- (>2-fold, p < 0.05) or down-regulated (≤2-fold, p < 0.05) in the BAFF-inhibited group. BAFF inhibition successfully reduced alloimmune responses through the reduction in alloantibody production and suppression of B cell differentiation and maturation. Our data suggest that BAFF suppression may serve as a useful target in desensitization therapy.

【 授权许可】

Unknown