Analysis of high and low responses to Staphylococcus aureus and interleukin 2 in human B lymphocytes.
Analysis of high and low responses to Staphylococcus aureus and interleukin 2 in human B lymphocytes.
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人 B 淋巴细胞对金黄色葡萄球菌和白细胞介素 2 的高低反应分析。
DOI：
10.1007/bf00920018
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发表时间：
1993
影响因子：
9.1
通讯作者：
Ashman,RF
中科院分区：
文献类型：
--
作者：
Peckham,DW;MowerJr,DA;Ashman,RF
固定的蛋白A-承载葡萄球菌（SAC）通过表面IG刺激人B细胞，而IL-2已被报道为增殖和分化提供足够的第二信号。用ELISPOT法计数分泌IgM、伊加和IgG的细胞，用吖啶橙子流式细胞术评估细胞周期进程，我们发现，相当少（5/13）的血清IG水平正常的健康志愿者的纯化B淋巴细胞不能响应SAC + IL-2分化为IG分泌细胞（ISC（IgM、伊加或IgG分泌细胞，<5%的输入B细胞）。高反应者通常形成10-35%的ISC。两组中表达IgG、伊加、IgM或IgD的B细胞比例无差异。通过平均连锁聚类分析，SAC/IL-2高应答者和低应答者被证明属于两个独立的群体相对于ISC。高反应者和低反应者倾向于在几个月内重复测试保持在同一组中，尽管观察到一些收敛。在SAC ± IL-2的存在下，低应答者也显示出比高应答者显著更少的晚期G1和S期进展。SAC + IL-2对B细胞上IL-2受体的诱导在高应答者中比在低应答者中大得多，如藻蓝蛋白缀合的IL-2的流式细胞术所示。然而，SAC + IL-2诱导转铁蛋白受体在低反应者中正常，表明在这些细胞中发生一些早期激活步骤。低应答B细胞通常在巨噬细胞和T细胞上清液存在下改善其应答。最后，绕过表面IG途径，使用抗CD 3激活的T细胞刺激B细胞，在低应答B细胞中产生正常分化。因此，临床正常个体的一个亚群具有B细胞，其不能表达IL-2受体，不能在体外对SAC + IL-2正常增殖和分化，但可以对通过T细胞、单核细胞及其产物的替代活化途径有良好的反应。
Fixed protein A-bearing staphylococci (SAC) stimulate human B cells via surface Ig, whereas IL-2 has been reported to provide a sufficient second signal for proliferation and differentiation. Using an ELISPOT assay to count cells secreting IgM, IgA, and IgG and flow cytometry with acridine orange to assess cell cycle progress, we have found that the purified B lymphocytes of a substantial minority (5/13) of healthy volunteers with normal serum Ig levels failed to differentiate to Ig secreting cells (ISC) in response to SAC + IL-2 (IgM, IgA, or IgG secreting cells, <5% of input B cells). High-responders generally formed 10–35% ISC. The proportions of B cells expressing IgG, IgA, IgM, or IgD were not different in the two groups. By average linkage cluster analysis, SAC/IL-2 high- and low-responders were shown to fall into two separate populations with respect to ISC. High- and low-responders tended to remain in the same group with repeated testing over several months, although some convergence was seen. The low-responders also showed significantly less advancement to late G1 and S phase than the high-responders, in the presence of SAC ± IL-2. Induction of IL-2 receptors on B cells by SAC + IL-2 was much greater in high-responders than in low-responders, as shown by flow cytometry with phycoerythrinconjugated IL-2. However, SAC + IL-2 induced transferrin receptors normally in low-responders, showing that some early activation steps occur in these cells. Low-responder B cells often improved their responses in the presence of macrophages and T cell supernatants. Finally, bypassing the surface Ig pathway using anti-CD3-activated T cells to stimulate B cells produced normal differentiation in low-responder B cells. Thus a subset of clinically normal individuals possesses B cells which fail to express IL-2 receptors, proliferate, and differentiate normallyin vitroin response to SAC + IL-2 yet can respond well to alternative activation pathways via T cells, monocytes, and their products.