Krenacs T, Rosendaal M
Department of Anatomy and Developmental Biology, University College London, England.
Dev Immunol. 1998;6(1-2):111-8. doi: 10.1155/1998/45913.
Intercellular channels called gap junctions enable multicellular organisms to exchange information rapidly between cells. Though gap junctions are held to be ubiquitous in solid tissues, we have only recently found them in the lymphoid organs. Functional direct cell-cell communication has now been confirmed by us and other groups in bone marrow, thymus, and in secondary lymphoid tissues. What functions do they serve in the lymphoreticular system where, so far, only cytokines/growth factors and adhesion molecules have been considered as regulators? Here we show evidence for and refer to published work about functional direct cell-cell communication through gap junctions in germinal center reactions and make proposals for their role in the immune response. We found a large amount of the connexin43 (Cx43) gap junctions in the germinal centers of secondary lymphoid follicles. Ultrastructurally and immunohistologically, most of the junctions were detected on the processes of follicular dendritic cells (FDC) enveloping nondividing centrocytes in the light zone of germinal centers where B-cell selection is thought to take place. Further support for this finding came by revealing the Cx43 mRNA in situ at the same location as the protein. On antigen challenge, gap junctions appeared on the FDC as they formed meshworks in germinal centers. In order to find out which germinal center cells communicate directly, we separated FDC-rich, low-density, B-cell fractions from human tonsil. In culture, we injected single FDC with the low-molecular-weight fluorescent dye, Lucifer Yellow (M(r) 457 Da), which passed between adjacent FDC and sometimes from FDC to B cells. Based on these findings and their assigned functions in other tissues, gap junctions may contribute to germinal center reactions in the following ways: (1) they may regulate follicle pattern formation by controlling FDC growth, (2) they may be involved in FDC-B-cell signaling contributing to the final rescue of selected B cells from apoptosis, and (3) they may enable FDC to work as a functional syncytium providing a cellular internet for integrating germinal center events. Data supporting these interpretations are briefly discussed.
被称为间隙连接的细胞间通道使多细胞生物能够在细胞之间快速交换信息。尽管间隙连接被认为在实体组织中普遍存在，但我们直到最近才在淋巴器官中发现它们。功能上的直接细胞间通讯现已得到我们和其他研究团队在骨髓、胸腺以及二级淋巴组织中的证实。在淋巴网状系统中，到目前为止，只有细胞因子/生长因子和黏附分子被视为调节因子，那么间隙连接在其中发挥着什么作用呢？在这里，我们展示了通过间隙连接在生发中心反应中进行功能上直接细胞间通讯的证据，并参考了已发表的相关研究工作，还对它们在免疫反应中的作用提出了建议。我们在二级淋巴滤泡的生发中心发现了大量的连接蛋白43（Cx43）间隙连接。在超微结构和免疫组织学上，大多数连接在生发中心明区包围着不分裂中心细胞的滤泡树突状细胞（FDC）的突起上被检测到，而B细胞选择被认为在此处发生。通过在与蛋白质相同的位置原位揭示Cx43 mRNA，进一步支持了这一发现。在抗原刺激下，间隙连接在生发中心形成网络时出现在FDC上。为了弄清楚哪些生发中心细胞直接进行通讯，我们从人扁桃体中分离出富含FDC的低密度B细胞组分。在培养过程中，我们用低分子量荧光染料路西法黄（分子量457 Da）注射单个FDC，该染料在相邻的FDC之间传递，有时还从FDC传递到B细胞。基于这些发现以及它们在其他组织中所具有的功能，间隙连接可能通过以下方式促进生发中心反应：（1）它们可能通过控制FDC生长来调节滤泡模式形成；（2）它们可能参与FDC - B细胞信号传导，有助于从凋亡中最终拯救被选择的B细胞；（3）它们可能使FDC作为一个功能合胞体发挥作用，为整合生发中心事件提供一个细胞网络。支持这些解释的数据将进行简要讨论。
