ACCUMULATION OF BROMODEOXYURIDINE-LABELED CELLS IN CENTRAL AND PERIPHERAL LYMPHOID ORGANS - MINIMAL ESTIMATES OF PRODUCTION AND TURNOVER RATES OF MATURE LYMPHOCYTES
ACCUMULATION OF BROMODEOXYURIDINE-LABELED CELLS IN CENTRAL AND PERIPHERAL LYMPHOID ORGANS - MINIMAL ESTIMATES OF PRODUCTION AND TURNOVER RATES OF MATURE LYMPHOCYTES
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DOI：
10.1002/eji.1830200812
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发表时间：
1990-08-01
影响因子：
5.4
通讯作者：
FREITAS, AA
中科院分区：
文献类型：
--
作者：
ROCHA, B;PENIT, C;FREITAS, AA
通过将体内结合溴脱氧尿苷（BrdUrd）与细胞表面标记和多参数流分析相结合，评估了中央和外周淋巴器官的每日淋巴细胞产量。每24小时至少产生10%的成熟T淋巴细胞和B淋巴细胞。然而，这些细胞群的动力学行为不同，因为成熟B细胞主要在骨髓的前体细胞室中产生，而大多数成熟T细胞发生在外周血。因此，外周扩增是成年小鼠成熟T细胞产生的主要机制。通过跟踪brdurd标记的细胞在外周血淋巴器官中的积累，我们发现每日淋巴细胞产生的后代足以每48小时更新30%-40%的外周血T和B细胞，显示出成熟淋巴细胞的高周转率。我们还研究了体内循环细胞BrdUrd标记的条件。我们发现，S期90%的骨髓和胸腺细胞被单次注射BrdUrd标记，而S期70%的T细胞和B细胞未能加入BrdUrd。需要特定的BrdUrd给药时间表来克服体内成熟细胞的低标记效率。然而，长期给药BrdUrd对驻留细胞有毒性作用。成熟细胞对BrdUrd掺入的低标记效率，以及其在长期给药过程中的潜在毒性，可能解释了研究淋巴细胞群体动力学所采用的不同策略所获得的有争议的结果。
Daily lymphocyte production in both central and peripheral lymphoid organs was evaluated by associating in vivo incorporation of bromodeoxyuridine (BrdUrd) with cell surface labeling and multi-parameter flow analysis. At least 10% of mature T and B lymphocytes are generated every 24 h. The kinetic behavior of these cell populations differs, however, in that mature B cells are generated predominantly in the precursor compartments of the bone marrow, while most mature T cell generation occurs at the periphery. Therefore, peripheral expansion is the major mechanism of mature T cell production in the adult mouse. By following the accumulation of BrdUrd-labeled cells in peripheral lymphoid organs we found that the progeny of the daily lymphocyte production was sufficient to renew 30%-40% of all peripheral T and B cells every 48 h, demonstrating a high turnover rate of mature lymphocytes. We also examined the conditions of BrdUrd labeling of cycling cells in vivo. We found that while > 90% of bone marrow and thymus cells in S phase were labeled with a single injection of BrdUrd, in peripheral lymphoid compartments 70% of T and B cells in S failed to incorporate BrdUrd. Particular schedules of BrdUrd administration were required to overcome the low labeling efficiency of mature cells in vivo. Prolonged BrdUrd administration, however, had toxic effects on resident cells. The low labeling efficiency of BrdUrd incorporation by mature cells, as well as its potential toxicity during prolonged administration, may explain controversial results obtained by the different strategies used to study lymphocyte population dynamics.