Establishment of strategies to regulate antibody-mediated rejection on the basis of B cell differentiation biology

通过活化T细胞依赖性B-2细胞和独立性B-1细胞产生的抗体现在被认为是急性和慢性排斥反应的重要介质。充分抑制这两种类型的B细胞活化对提高同种异体移植物存活率是重要的。然而，B-1/B-2细胞分化对各种免疫抑制剂的敏感性仍有待阐明。为了解决这个问题，在本研究中，我们建立了体外和体内B细胞活化模型，其中可以诱导分化为B-1a、B-1 B和B-2细胞。利用这些模型，我们评估了各种免疫抑制药物和我们新开发的抗CD 1d抗体对B细胞活化的敏感性和特异性。

Antibodies produced through the activation of T cell-dependent B-2 cells and independent B-1 cells are now appreciated as important mediators of acute and chronic rejection. It is important to suppress sufficiently both type of B cell activation for improvement of allograft survival. However, the sensitivity of B-1/B-2 cell differentiation to various immunosuppressants still remained to be elucidated. To address this issue, in the present study, we have established in vitro and in vivo B cell activation models, in which the differentiation to B-1a, B-1b, and B-2 cells can be induced. By use of those models, we have evaluate the sensitivity and specificity of various immunosuppressive drugs and anti-CD1d antibody newly developed by us to B cell activation.