Kinetics of germinal center development in lymph nodes of young and aging immune mice.
Kinetics of germinal center development in lymph nodes of young and aging immune mice.
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年轻和衰老免疫小鼠淋巴结生发中心发育的动力学。
DOI：
10.1002/ar.1092270411
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Tew,JJ
中科院分区：
文献类型：
--
作者：
Szakal,AK;Taylor,JK;Smith,JP;Kosco,MH;Burton,GF;Tew,JJ
最近的研究结果表明，老年小鼠的生发中心缺乏，至少部分是由于负责将抗原转运到淋巴结（滤泡）的机制缺陷以及随后滤泡树突状细胞（FDCs）的抗原保留网（ARR）受损。本研究旨在观察抗原转运和ARR缺陷的老年小鼠淋巴结生发中心发育的动力学。在6、8周龄和23月龄辣根过氧化物酶（HRP）免疫C57 BL/6小鼠的腘（PLN）和腋窝（AXLN）淋巴结中监测生殖中心发育。利用生发中心B细胞与花生凝集素（PNA）的选择性结合，在用8 μg HRP足垫激发后0、15 min、1、3、5和10天时，用PNA-过氧化物酶结合物进行组织化学标记后，在连续振动切片机切片中鉴定生发中心。为了跟踪预先存在的（环境抗原诱导的）生发中心的命运和新生的（HRP诱导的）生发中心的发展，必须区分这些生发中心。因此，与HRP保留（过氧化物酶阳性）ARR相关的PNA阳性生发中心被确定为新生生发中心，与过氧化物酶阳性ARR无关的生发中心被归类为既存生发中心。PNA阳性生发中心的动力学分析表明：（1）预先存在的环境诱导的生发中心在第3天解离并消失，如抗原注射后其数量下降所示;生发中心解离过程不受老化影响。(2)新生生发中心出现的潜伏期与原有生发中心消失的持续时间大致相等（约3天）。(3)在年轻淋巴结中，从头HRP诱导的生发中心的数量和大小在整个实验期间增加，但在老年小鼠中，这些参数被抑制，导致生发中心显著缺陷。(4)在年轻小鼠和应答老年小鼠中，保留HRP的ARR与从头诱导的生发中心的比例为1：1。该比例不受老化影响。这一发现支持了ARR中抗原保留是生发中心发育所必需的概念。这些观察结果支持了我们的假设，即生发中心的发育至少部分取决于正常的抗原转运，这表明在抗原转运相关ARR缺陷和核小体缺陷的老年小鼠中，生发中心的发育受损。
Recent findings imply that germinal center paucity in old mice, at least in part, results from a defect in the mechanisms responsible for the transport of antigens to lymphoid nodules (follicles) and the consequent impairment of the antigen retaining reticulum (ARR) of follicular dendritic cells (FDCs). The present objective was to observe the kinetics of lymph node germinal center development in old mice having antigen transport and ARR deficits. Germinal center development was monitored in popliteal (PLN) and axillary (AXLN) lymph nodes of 6–;8 wk and 23‐mo‐old horseradish peroxidase (HRP) immune C57BL/6 mice. Using the selective binding of germinal center B cells for peanut agglutinin (PNA), germinal centers were identified in serial vibratome sections following histochemical labeling with PNA‐peroxidase conjugates at times 0, 15 min, 1, 3, 5, and 10 days after footpad challenge with 8 μg HRP. To follow the fate of preexisting (environmental antigen‐induced) germinal centers and the development of de novo (HRP‐induced) germinal centers, it was essential to distinguish between these germinal centers. Accordingly, PNA positive germinal centers associated with HRP‐retaining (peroxidase positive) ARR were identified as de novo germinal centers and germinal centers not associated with a peroxidase positive ARR were classified as preexisting germinal centers. Kinetic analysis of PNA positive germinal centers showed the following: (1) Preexisting, environmentally‐induced germinal centers dissociated and disappeared by day 3 as indicated by a decline in their numbers after antigen injection; the process of germinal center dissociation remained unaffected by aging. (2) The latency of de novo germinal center appearance was approximately equal in duration (∼3 days) to the disappearance of preexisting germinal centers. (3) The number and size of de novo HRP‐induced germinal centers increased through the experimental period in young lymph nodes, but in old mice these parameters were depressed, resulting in a significant germinal center deficit. (4) The ratio of HRP‐retaining ARR to de novo induced germinal centers was 1:1 in young and responder old mice. This ratio was not affected by aging. This finding favored the concept that antigen retention in ARR is a requirement of germinal center development. The observations supported our hypothesis that germinal center development, at least in part, depends on a normal antigen transport by showing that in aged mice with defective antigen transport‐related ARR and iccosome deficits there is an impaired development of germinal centers.