THE ROLE OF CELLULAR COMPETITION IN B-CELL SURVIVAL AND SELECTION OF B-CELL REPERTOIRES

THE ROLE OF CELLULAR COMPETITION IN B-CELL SURVIVAL AND SELECTION OF B-CELL REPERTOIRES
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DOI:
10.1002/eji.1830250636
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发表时间:
1995-06-01
影响因子:
5.4
通讯作者:
GRANDIEN, A
GRANDIEN, A
中科院分区:
医学3区
文献类型:
--
作者:
FREITAS, AA;ROSADO, MM;GRANDIEN, A

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我们研究了用来自同源或 Ig 转基因 (TG) 小鼠的骨髓以不同比例混合重建的受辐射小鼠的不同 B 细胞的竞争性增殖。我们发现重建后,不同嵌合体中回收的 B 细胞数量相似,并且与注射细胞的比例无关。在宿主 TG 和非 TG 细胞的嵌合体中,供体细胞谱系的相对代表性与接种物中存在的比例不同,即在外围,优先选择非 TG 细胞。非 TG 细胞的选择仅在种群增长停滞时发生,即当资源变得有限并且竞争开始运作时。非TG细胞的选择取决于表面Ig表达,选择它们是因为它们具有更长的存活时间。最后,同一 B 细胞群的预期寿命因存在的第二个细胞群而异。目前的结果表明,第二个细胞群的存在可以改变(干扰)每个 B 细胞克隆的寿命和群体大小,这证明了 B 细胞之间存在细胞竞争。我们的研究结果证实了细胞竞争在 B 细胞库选择中的作用,以及在没有抗原刺激的情况下 B 细胞选择层次结构的存在。讨论了细胞竞争对我们理解免疫系统的影响。
We studied the competitive repopulation by different B cells of irradiated mice reconstituted with bone marrow from either congenic or Ig-transgenic (TG) mice mixed at different ratios. We found that after reconstitution, the number of B cells recovered in the different chimeras is similar and independent of the ratio of injected cells. In chimeras hosting TG and non-TG cells, the relative representation of the donor cell lineages diverges from the ratios present in the inoculum, i.e. at the periphery, non-TG cells are preferentially selected. Selection of non-TG cells only occurs when population growth plateaus, i.e. when resources become limiting and competition starts to operate. Selection of non-TG cells depends on surface Ig expression, and they are selected because they have a longer survival. Finally, the life-expectancy of the same B cell population differs depending upon the second population present. The present results show that the life-span and the population size of each B cell clone can be altered (interfered with) by the presence of a second cell population, demonstrating the existence of cellular competition among B cells. Our findings establish the role of cellular competition in the selection of B cell repertoires and the existence of a hierarchy of B cell selection in the absence of antigenic stimulation. The implications of cellular competition on our understanding of the immune system are discussed.