Belkin Danny, Torkar Michaela, Chang Chiwen, Barten Roland, Tolaini Mauro, Haude Anja, Allen Rachel, Wilson Michael J, Kioussis Dimitris, Trowsdale John
Immunology Division, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
J Immunol. 2003 Sep 15;171(6):3056-63. doi: 10.4049/jimmunol.171.6.3056.
To generate an experimental model for exploring the function, expression pattern, and developmental regulation of human Ig-like activating and inhibitory receptors, we have generated transgenic mice using two human genomic clones: 52N12 (a 150-Kb clone encompassing the leukocyte Ig-like receptor (LILR)B1 (ILT2), LILRB4 (ILT3), and LILRA1 (LIR6) genes) and 1060P11 (a 160-Kb clone that contains ten killer cell Ig-like receptor (KIR) genes). Both the KIR and LILR families are encoded within the leukocyte receptor complex, and are involved in immune modulation. We have also produced a novel mAb to LILRA1 to facilitate expression studies. The LILR transgenes were expressed in a similar, but not identical, pattern to that observed in humans: LILRB1 was expressed in B cells, most NK cells, and a small number of T cells; LILRB4 was expressed in a B cell subset; and LILRA1 was found on a ring of cells surrounding B cell areas on spleen sections, consistent with other data showing monocyte/macrophage expression. KIR transgenic mice showed KIR2DL2 expression on a subset of NK cells and T cells, similar to the pattern seen in humans, and expression of KIR2DL4, KIR3DS1, and KIR2DL5 by splenic NK cells. These observations indicate that linked regulatory elements within the genomic clones are sufficient to allow appropriate expression of KIRs in mice, and illustrate that the presence of the natural ligands for these receptors, in the form of human MHC class I proteins, is not necessary for the expression of the KIRs observed in these mice.
为了构建一个用于探索人类免疫球蛋白样激活和抑制性受体的功能、表达模式及发育调控的实验模型，我们利用两个人类基因组克隆构建了转基因小鼠：52N12（一个150kb的克隆，包含白细胞免疫球蛋白样受体（LILR）B1（ILT2）、LILRB4（ILT3）和LILRA1（LIR6）基因）和1060P11（一个160kb的克隆，包含10个杀伤细胞免疫球蛋白样受体（KIR）基因）。KIR和LILR家族均编码于白细胞受体复合物中，并参与免疫调节。我们还制备了一种针对LILRA1的新型单克隆抗体，以促进表达研究。LILR转基因在小鼠中的表达模式与人类相似但不完全相同：LILRB1在B细胞、大多数NK细胞和少数T细胞中表达；LILRB4在一个B细胞亚群中表达；在脾脏切片上，LILRA1在围绕B细胞区域的一圈细胞上被发现，这与其他显示单核细胞/巨噬细胞表达的数据一致。KIR转基因小鼠在一部分NK细胞和T细胞上显示出KIR2DL2表达，类似于人类中的模式，并且脾脏NK细胞表达KIR2DL4、KIR3DS1和KIR2DL5。这些观察结果表明，基因组克隆中的连锁调控元件足以使KIR在小鼠中实现适当表达，并说明这些受体的天然配体（以人类MHC I类蛋白的形式存在）对于在这些小鼠中观察到的KIR表达并非必需。
