Paramithiotis E, Jacobsen K A, Ratcliffe M J
Department of Microbiology and Immunology, McGill University, Montréal, Québec, Canada.
J Exp Med. 1995 Jan 1;181(1):105-13. doi: 10.1084/jem.181.1.105.
The vast majority of lymphocytes generated daily in the chicken bursa of Fabricius do not emigrate to the periphery but die in situ. Apoptotic cells in the bursa can be readily detected by the presence of fragmented DNA and by the large numbers of condensed cellular nuclei observed by electron microscopy. Consequently, most newly generated lymphocytes die by programmed cell death. We show that bursal cells divide rapidly and apoptotic cells are derived from rapidly dividing precursors. Analysis of the phenotype of bursal cells undergoing apoptosis demonstrated that cell death does not occur in the most mature bursal cell population and is therefore not random. High levels of surface Ig are expressed on bursal cells entering S phase of the cell cycle. In contrast, bursal cells in the early stages of apoptosis in vivo express very low to undetectable levels of surface Ig but were unequivocally confirmed as being of the B lineage by polymerase chain reaction (PCR) detection of rearranged Ig genes. Bursal cells induced to undergo apoptosis in vitro express high levels of surface Ig demonstrating that induction of apoptosis does not in itself induce a loss of surface Ig expression. Consequently, loss of surface Ig expression precedes bursal cell death by apoptosis in vivo, suggesting that maintenance of a threshold level of surface Ig may be a requirement for the continued progression of chicken B lymphocyte development in the bursa.
鸡法氏囊中每天产生的绝大多数淋巴细胞不会迁移到外周，而是原位死亡。法氏囊中凋亡细胞可通过DNA片段化的存在以及电子显微镜下观察到的大量凝聚细胞核轻松检测到。因此，大多数新产生的淋巴细胞通过程序性细胞死亡而死亡。我们发现法氏囊细胞快速分裂，凋亡细胞来源于快速分裂的前体细胞。对正在经历凋亡的法氏囊细胞表型分析表明，细胞死亡并非发生在最成熟的法氏囊细胞群体中，因此不是随机的。进入细胞周期S期的法氏囊细胞表面表达高水平的免疫球蛋白（Ig）。相反，体内处于凋亡早期的法氏囊细胞表面Ig表达水平极低甚至无法检测到，但通过聚合酶链反应（PCR）检测重排的Ig基因明确证实它们属于B淋巴细胞系。体外诱导凋亡的法氏囊细胞表面表达高水平的Ig，表明凋亡的诱导本身并不会导致表面Ig表达的丧失。因此，在体内，表面Ig表达的丧失先于法氏囊细胞通过凋亡死亡，这表明维持表面Ig的阈值水平可能是鸡B淋巴细胞在法氏囊中持续发育的必要条件。
