CD5-positive and CD5-negative human B cells converge to an indistinguishable population on signalling through B-cell receptors and CD40
CD5-positive and CD5-negative human B cells converge to an indistinguishable population on signalling through B-cell receptors and CD40
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DOI：
10.1046/j.1365-2567.2000.00098.x
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发表时间：
2000-10-01
期刊：
影响因子：
6.4
通讯作者：
Gordon, J
中科院分区：
文献类型：
--
作者：
Gagro, A;Mccloskey, N;Gordon, J
B细胞上的CD 5是否标志着一个功能上不同于常规CD 5阴性（CD 5（neg））成人群体的亚群，或者更多地是一个活化的指标，仍然存在争议。在此，我们研究了是否可以根据它们对替代信号的响应来区分CD 5阳性（CD 5（pos））和CD 5（neg）B细胞，所述替代信号旨在体外模拟T细胞依赖性（TD）和T细胞非依赖性（TI）在体内与抗原的接触：在脐带血中发现的主要是CD 5（阳性）B细胞群，从扁桃体中阳性选择的CD 5 B细胞及其CD 5（阴性）对应物，比较了新生儿B细胞表现出与成人CD 5（pos）B细胞几乎相同的表型，其特征在于均匀的免疫球蛋白M（IgM）、免疫球蛋白D（IgD）、CD 23和CD 44共表达。当在CD 32转染的小鼠L细胞上以高密度维持抗IgM以模拟TI应答或在携带CD 40配体（CD 40 L）的L细胞（有或没有捕获的抗IgM）上以模拟TD遭遇时，在所有三个群体中DNA合成被刺激到相似的程度。聚焦于CD 5和CD 23，我们发现，尽管传递的信号促进了不同的表达谱，但在每种活化条件下，成人CD 5（阳性）和CD 5（阴性）B细胞出现的表型非常相似。新生儿B细胞在CD 40信号后表现出比成人CD 5（pos）B细胞更大的CD 5表达减少，但除此之外，两个群体的表现也相似。将白细胞介素-4（IL-4）加入到通过表面IgM和CD 40共刺激细胞的培养物中，导致CD 5表达完全丧失和相应的CD 23过表达，与研究的人群无关。在体外，CD 5（阳性）和CD 5（阴性）B细胞对替代TD或TI信号的几乎相同的反应以及它们向不可区分的表型的会聚完全支持CD 5是活化的波动标记物，而不是其描绘功能不同的子集。
Whether CD5 on B cells marks a subset functionally distinct from the conventional CD5 negative (CD5(neg)) adult population or is more an indicator of activation, remains contentious. Here we have investigated whether CD5 positive (CD5(pos)) and CD5(neg) B cells can be distinguished in terms of their response to surrogate signals aimed to model, in vitro, T-cell dependent (TD) and T-independent (TI) encounters with antigen in vivo: the predominantly CD5(pos) B-cell population found in cord blood, CD5 B cells positively selected from tonsils and their CD5(neg) counterparts, were compared. Neonatal B cells displayed a near-identical phenotype to that of adult CD5(pos) B cells, being characterized by uniform immunoglobulin M (IgM), immunoglobulin D (IgD), CD23 and CD44 coexpression. When cultured with anti-IgM maintained at high density on CD32-tranfected mouse L cells to model TI responses or on CD40 ligand (CD40L)-bearing L cells (with or without captured anti-IgM) to model TD encounters, DNA synthesis was stimulated to a similar extent in all three populations. Focusing on CD5 and CD23, we found that - although the signals delivered promoted distinct profiles of expression - under each condition of activation, the phenotypes that emerged for adult CD5(pos) and CD5(neg) B cells were remarkably similar. Neonatal B cells displayed a greater diminution in CD5 expression than adult CD5(pos) B cells following CD40 signals but otherwise the two populations again behaved similarly. The inclusion of interleukin-4 (IL-4) to cultures where cells were costimulated via surface (s)IgM and CD40 resulted in a complete loss of CD5 expression and a corresponding hyperexpression of CD23, irrespective of the population studied. The near-identical response of CD5(pos) and CD5(neg) B cells to surrogate TD or TI signals in vitro and their convergence to indistinguishable phenotypes is wholly supportive of CD5 being a fluctuating marker of activation rather than it delineating functionally distinct subsets.