Differentiation-induction of antibody producing human B cells from cord blood CD34+ cells in mice for generating monoclonal antibody used in clinical therapy

单克隆抗体从各种动物模型中被认为是有用的临床治疗方法。然而，尽管人类/小鼠嵌合体抗体是可用的，但来自人B细胞的治疗性抗体尚未用于临床领域。为了获得人B细胞产生的单克隆抗体，本研究试图利用脐带血CD34+细胞在免疫缺陷小鼠中重建人免疫系统。我们得到了以下结果。1)人CD34+细胞在小鼠胸腺上皮细胞与人CD34+细胞重新聚集的体内RTOC中发育成具有细胞因子产生能力的成熟T细胞。2) NOG小鼠在体内重建T细胞发育可能是因为它们完全缺乏NK细胞活性以及T细胞和B细胞。3)体内处理抗cd40抗体可诱导抗原特异性抗体升高，但IgG类较低。4)注射到NOG小鼠体内的CB CD34+细胞主要在脾脏发育为CD5+B细胞。5)利用嵌合体抗erbb -2抗体和疟疾患者血清，鉴定抗原表位。这些肽将用于免疫接受DBCD34+细胞的NOG小鼠。

Monoclonal antibodies are known to be useful as the clinical therapy from various animal models. However, therapeutic antibodies derived human B cells have not used in the clinical field although human/mouse chimera antibodies are available. In order to obtain monoclonal antibodies produced by human B cells, we tried to reconstitute human immune system in the immuno-deficient mice from CD34+ cells in cord blood (CB) in this study. We obtained the following results. 1) Human CD34+ cells develop into mature T cells with cytokine producing ability in the in vivo RTOC in which mouse thymic epithelial cells are reaggregated with human CD34+cells. 2) NOG mice are useful to reconstitute T cell development in vivo probably because they lack completely NK cell activity as well as T and B cells. 3) In vivo treatment of anti-CD40 antibody induces the increase of antigen specific antibody although IgG class is low. 4) CB CD34+ cells injected into NOG mice mainly develop into CD5+B cells in the spleen. 5) Using chimera anti-erbB-2 antibody and serum from malaria patients, antigen epitopes were identified. These peptides are going to use for immunizing NOG mice receiving DBCD34+ cells.