MacLennan I C, Liu Y J, Johnson G D
Department of Immunology, University of Birmingham, U.K.
Immunol Rev. 1992 Apr;126:143-61. doi: 10.1111/j.1600-065x.1992.tb00635.x.
Germinal centers develop in follicles during TD antibody responses in the first 3 wk following each immunization. In primary responses to protein-based antigens, T-cell help is limiting, follicles develop towards the end of the 1st wk from immunization and the size of the follicular response in relatively small. When T-cell help is provided the primary B-cell response in follicles is much larger, B cells start to proliferate in follicles within a few hours of immunization and reach peak size 3-4 d later. Available evidence suggests that virgin B cells that colonize follicles to form germinal centers must first be activated by antigen outside follicles, probably in T zones. Memory B cells also proliferate in follicles and they can do so without first being activated outside follicles. Germinal center formation consists of an initial phase of exponential proliferation of B cells within the follicular dendritic cell network. After a single immunization the follicular response is oligoclonal and on average only 3 cells colonize each follicle. In responses to hapten-protein in rats primed previously with the carrier protein these 3 cells increase to around 10(4) cells in 3 d with a cell cycle time of about 6 h. At the end of the period of exponential growth of B blasts, the classical structure of germinal centers emerges. The B blasts become centroblasts in the dark zone of the germinal center which develops at that pole of the FDC network nearer the T zones. The centroblasts are still in rapid cell cycle but do not more than sustain their numbers. The rest of their progeny move to the heart of the FDC network where they come out of cell cycle as centrocytes. Evidence is cited which indicates that somatic mutation occurs in the Ig V-region genes of centroblasts and that centrocytes are selected on the basis of their ability to respond to antigen held on FDC. Centrocytes not receiving this antigen-dependent signal kill themselves by apoptosis. Centrocytes positively selected by interaction with antigen on FDC receive further signals which induce the cells to differentiate to become either plasma cells or memory B cells. The nature of some of these differentiation signals is described. It is shown that proliferation, selection and differentiation occur within germinal centers in distinct micro-environments.(ABSTRACT TRUNCATED AT 400 WORDS)
在每次免疫后的前3周，生发中心在TD抗体应答过程中于滤泡内形成。在对基于蛋白质的抗原的初次应答中，T细胞辅助是有限的，滤泡在免疫后第1周快结束时开始发育，且滤泡反应的规模相对较小。当有T细胞辅助时，滤泡内的B细胞初次应答会大得多，B细胞在免疫后数小时内开始在滤泡中增殖，并在3 - 4天后达到最大规模。现有证据表明，定殖于滤泡以形成生发中心的处女B细胞必须首先在滤泡外被抗原激活，可能是在T细胞区。记忆B细胞也在滤泡中增殖，并且它们无需首先在滤泡外被激活就能增殖。生发中心的形成包括B细胞在滤泡树突状细胞网络内呈指数增殖的初始阶段。单次免疫后，滤泡反应是寡克隆性的，平均每个滤泡只有3个细胞定殖。在用载体蛋白预先致敏的大鼠对半抗原 - 蛋白质的应答中，这3个细胞在3天内增加到约10⁴个细胞，细胞周期约为6小时。在B母细胞指数增长期结束时，生发中心的经典结构出现。B母细胞在生发中心的暗区成为中心母细胞，生发中心在滤泡树突状细胞网络靠近T细胞区的那一极发育。中心母细胞仍处于快速细胞周期，但数量不再增加。它们其余的子代细胞迁移到滤泡树突状细胞网络的核心区域，在那里它们作为中心细胞退出细胞周期。有证据表明，中心母细胞的Ig V区基因会发生体细胞突变，并且中心细胞是根据它们对抗原呈递于滤泡树突状细胞上的抗原的应答能力来被选择的。未接收到这种抗原依赖性信号的中心细胞通过凋亡自杀。通过与滤泡树突状细胞上的抗原相互作用而被阳性选择的中心细胞会接收到进一步的信号，这些信号诱导细胞分化为浆细胞或记忆B细胞。文中描述了其中一些分化信号的性质。结果表明，增殖、选择和分化在生发中心内不同的微环境中发生。（摘要截断于400字）
