The production of red blood cell alloantibodies in mice transfused with blood from transgenic Fyb-expressing mice
The production of red blood cell alloantibodies in mice transfused with blood from transgenic Fyb-expressing mice
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DOI：
10.1111/j.1537-2995.2006.00966.x
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发表时间：
2006-10-01
期刊：
影响因子：
2.9
通讯作者：
Baldwin, William M.
中科院分区：
文献类型：
--
作者：
Campbell-Lee, Sally A.;Liu, Jinhuan;Baldwin, William M.
小鼠模型将有助于确定可以操纵哪些免疫机制来治疗或防止对多种或广泛表达的抗原致敏的患者的红细胞(RBC)异基因免疫。表达Duffy(Fy)血型人FY(B)抗原的转基因小鼠(B6CBAF1/J-TG-FY(B))是捐赠者。受体B6CBA-F1小鼠每周接受四次静脉(IV)输血：0.3mL洗过的去黄褐色的RBC或0.3mL带脾细胞的RBC。以供体小鼠红细胞为靶细胞，用流式细胞仪检测受者血清中免疫球蛋白M(IgM)和免疫球蛋白G(IgG)的滴度。受者血清样本也被用来对抗不同FY表型的人红细胞。此外，利用生物素标记的FY(B)转基因小鼠红细胞在同种异体免疫小鼠中进行了RBC存活研究。B6CBA-F1小鼠接受洗涤的去黄褐色去毛红细胞后，首先产生IgM，然后是针对转基因小鼠FY(B)阳性红细胞的同种异体抗体。与脾细胞混合的FY(B)阳性红细胞的受者也产生了IgM和Ig G同种抗体，但比洗涤的淡黄色去毛红细胞的受者要慢。血清样本显示出FY3、FY(B)和Fy6的特异性。在输血后24小时，输注的红细胞存活率明显下降，在缺乏FY抗原的小鼠中，静脉输注可以诱导产生抗FY同种抗体。单独输注红细胞足以刺激B6CBA-F1受体小鼠产生同种异体抗体。在致敏小鼠中，输注FY(B)阳性红细胞的存活率降低。该模型可用于RBC同种异体免疫的进一步研究。
A murine model would be useful to identify which immune mechanisms could be manipulated to treat or prevent red blood cell (RBC) alloimmunization in patients who become sensitized to multiple or widely expressed antigens.Transgenic mice (B6CBAF1/J-Tg-Fy(b)) expressing the human Fy(b) antigen of the Duffy (Fy) blood group were donors. Recipient B6CBA-F1 mice received four weekly intravenous (IV) transfusions: either 0.3 mL of washed buffy coat-depleted RBCs or 0.3 mL of RBCs with spleen cells. Titers of immunoglobulin M (IgM) and immunoglobulin G (IgG) were measured in recipient serum samples by flow cytometry with RBCs from donor mice as target cells. Recipient serum samples were also tested against human RBCs of various Fy phenotypes. Additionally, RBC survival studies were performed in alloimmunized mice utilizing biotin-labeled Fy(b) transgenic mouse RBCs.B6CBA-F1 mice receiving washed buffy coat-depleted RBCs first made IgM, followed by IgG alloantibodies to transgenic mouse Fy(b)-positive RBCs. Recipients of Fy(b)-positive RBCs mixed with spleen cells also produced IgM and IgG alloantibodies, but at a slower rate than recipients of washed buffy coat-depleted RBCs. Serum samples showed specificity for Fy3, Fy(b), and Fy6. Decreased survival of transfused RBCs was evident at 24 hours after transfusion.It is possible to elicit the formation of anti-Fy alloantibodies by IV transfusion in mice that lack Fy antigens. The transfusion of RBCs alone was adequate to stimulate alloantibody production in B6CBA-F1 recipient mice. The survival of transfused Fy(b)-positive RBCs is diminished in sensitized mice. This model will be useful in further studies of RBC alloimmunization.