Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/ijms22020861
Keywords
HLA; A2 transgenic mice; sensitization; skin allograft; BAFF; donor-specific antibody
Funding
- Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [HI20C0317]
- Korean Society of Nephrology (Chong Kun Dang, 2017)
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Inhibition of BAFF can reduce HLA.A2-specific IgG, alter the proportions of B cells in the bone marrow and spleen, and decrease specific immune responses. This suggests that BAFF suppression may be a useful target for desensitization therapy research and development.
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 (Delta-13.62 vs. Delta 27.07, 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.
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