Ectopic B-cell clusters that infiltrate transplanted human kidneys are clonal
Ectopic B-cell clusters that infiltrate transplanted human kidneys are clonal
复制标题
DOI：
10.1073/pnas.1101148108
复制
发表时间：
2011-04-05
影响因子：
11.1
通讯作者：
Lerner, Richard A.
中科院分区：
文献类型：
--
作者：
Cheng, Julong;Torkamani, Ali;Lerner, Richard A.
B细胞及其免疫球蛋白产物参与移植肾的排斥反应，其中一个有趣的特征是异体移植物中存在生发中心样的B细胞簇。我们在这里报道，这些浸润的B细胞的免疫球蛋白库受到高度限制，并且簇内的B细胞是克隆的。从个体患者的浸润B细胞中获得的抗体文库意外地显示，每个患者都利用一组特定的显性种系基因以及显性互补决定区3。对同一患者的肾脏和外周血进行比较，发现两个区室的免疫球蛋白基因均有优势克隆，但又有所不同。浸润肾脏的淋巴细胞表达免疫球蛋白基因体细胞重组机制，通常仅限于生发中心和淋巴瘤中高度活化的淋巴细胞。慢性感染中不可避免的抗原驱动与同种异体移植物中不可避免的抗原驱动可以类比，两者都可能导致显性b细胞克隆的出现，甚至淋巴细胞恶性肿瘤。
B cells and their immunoglobulin products participate in allograft rejection of transplanted human kidneys in which an interesting feature is the presence of a germinal center like B-cell clusters in the allograft. We report here that the immunoglobulin repertoires of these infiltrating B cells are highly restricted and the B cells within a cluster are clonal. Antibody libraries made from the infiltrating B cells of individual patients unexpectedly revealed that each patient utilizes a particular set of dominant germ line genes as well as dominant complementarity determining region 3. Comparison of kidney and peripheral blood from the same patient showed that the immunoglobulin genes from both compartments had dominant clones, but they differed. The lymphocytes that infiltrate the kidneys express the immunoglobulin gene somatic recombination machinery usually restricted to highly activated lymphocytes in germinal centers and lymphomas. An analogy can be made between the inescapable antigenic drive in chronic infection versus that in an allograft, both of which may lead to emergence of dominant B-cell clones and even lymphoid malignancy.