Transplantation Unit, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Cell Transplant. 2014 Jan;23(1):51-8. doi: 10.3727/096368912X658962. Epub 2012 Nov 27.
A short course of anti-CD45RB leads to long-term islet allograft survival and donor-specific tolerance in approximately half of immunocompetent mice. We have previously demonstrated that anti-CD45RB antibody-mediated tolerance requires B-cells for cardiac allograft survival. We therefore asked whether B-cells were also required for anti-CD45RB antibody-mediated survival of islets. Unexpectedly, we found that nearly 100% of islet allografts survive long term in B-cell-deficient mice. Similarly, B-cell depletion by anti-CD22/cal augmented anti-CD45RB-mediated tolerance when administered pretransplant, although it had no effect on tolerance induction when administered posttransplant. Our results demonstrate that the role of B-cells in promoting tolerance with anti-CD45RB is graft specific, promoting tolerance in cardiac grafts but resisting tolerance in islet transplantation. These findings may help elucidate the varied action of B-cells in promoting tolerance versus rejection.
抗 CD45RB 短疗程治疗可导致近一半免疫功能正常的小鼠长期胰岛移植物存活和供体特异性耐受。我们之前的研究表明，抗 CD45RB 抗体介导的耐受需要 B 细胞才能实现心脏移植物存活。因此，我们想知道 B 细胞是否也需要抗 CD45RB 抗体介导的胰岛存活。出乎意料的是，我们发现近 100%的胰岛同种异体移植物在 B 细胞缺陷小鼠中可长期存活。同样，在移植前给予抗 CD22/cal 耗尽 B 细胞可增强抗 CD45RB 介导的耐受，尽管在移植后给予时对诱导耐受没有影响。我们的研究结果表明，B 细胞在抗 CD45RB 促进耐受中的作用具有移植物特异性，可促进心脏移植物的耐受，但抵抗胰岛移植的耐受。这些发现可能有助于阐明 B 细胞在促进耐受与排斥中的不同作用。
