A DEVELOPMENTAL SWITCH IN B-LYMPHOPOIESIS
A DEVELOPMENTAL SWITCH IN B-LYMPHOPOIESIS
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DOI：
10.1073/pnas.88.24.11550
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发表时间：
1991-12-01
影响因子：
11.1
通讯作者：
HAYAKAWA, K
中科院分区：
文献类型：
--
作者：
HARDY, RR;HAYAKAWA, K
B和T淋巴细胞在胎儿和成人生命期间由造血干细胞产生。一个关键的未解决问题是，胎儿和成年动物的淋巴细胞生成分化途径是否相同，或者它们是否存在差异，类似于红细胞生成中的血红蛋白转换。我们在这里报告说，发展开关发生在B淋巴细胞。我们分离了“pro-B”细胞（即，已经启动但未完成重链基因重排的细胞），并研究了它们在体外和体内产生的B细胞后代。大多数来自胎儿肝脏的细胞，但很少来自成人骨髓的细胞，表达CD 5。此外，胎儿pro-B细胞未能产生细胞表达高水平的IgD在严重的联合免疫缺陷小鼠，而成人pro-B细胞产生的CD 5-细胞轴承IgD的水平相当的大部分细胞在脾脏中的成年小鼠。因此，与成年动物骨髓中处于相当分化阶段的细胞相比，妊娠第16天小鼠胎肝中所有定向B祖细胞产生表型不同的子代。我们的结论是，在早期胎儿发育的B系祖细胞的队列致力于分化途径不同，在成人中看到的。
B and T lymphocytes are generated from hematopoietic stem cells during both fetal and adult life. A critical unresolved issue is whether the differentiation pathways in lymphopoiesis are the same in fetal and adult animals or whether they differ, similar to the hemoglobin switch in erythropoiesis. We report here that a developmental switch occurs in B lymphopoiesis. We isolated "pro-B" cells (i.e., cells that have initiated, but not completed, heavy-chain gene rearrangement) from fetal and adult sources and investigated their B-cell progeny generated both in vitro and in vivo. Most of the cells from fetal liver, but few from adult bone marrow, expressed CD5. Further, fetal pro-B cells failed to generate cells expressing high levels of IgD in severe combined immunodeficiency mice, whereas adult pro-B cells gave rise to CD5-cells bearing IgD at levels comparable to the bulk of cells in the spleen of adult mice. Thus, all committed B progenitors in fetal liver of day 16 gestation mice give rise to phenotypically distinct progeny when compared to cells at a comparable differentiation stage in the bone marrow of adult animals. We conclude that the cohort of B-lineage progenitors in early fetal development is committed to a differentiation pathway distinct from that seen in the adult.