Antigen-specific B cells preferentially induce CD4+ T cells to produce IL-4.
Antigen-specific B cells preferentially induce CD4+ T cells to produce IL-4.
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DOI：
10.4049/jimmunol.158.9.4171
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发表时间：
1997-05
影响因子：
4.4
通讯作者：
A. Macaulay;R. DeKruyff;C. Goodnow;D. Umetsu
中科院分区：
文献类型：
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作者：
A. Macaulay;R. DeKruyff;C. Goodnow;D. Umetsu
B 细胞的 Ag 呈递在调节细胞因子谱受限的 T 细胞发育中的作用仍存在争议。在本报告中，我们比较了初始多克隆 B 细胞、初始 Ag 特异性 B 细胞（来自 Ig 受体转基因小鼠）或脾贴壁细胞 (SAC) 的 Ag 呈递，并检查了这些细胞影响 CD4+ T 细胞产生细胞因子的能力。新鲜分离的初始 B 细胞刺激 T 细胞旺盛增殖和非常强的 T 细胞细胞因子反应，但仅当与 B 细胞 Ig 受体（同源 Ag）识别的 Ag 一起培养时，而不是与非同源 Ag 一起培养时。在这些条件下，由 Ig 受体介导的 Ag 内吞作用激活的 B 细胞诱导初始 CD4+ T 细胞和 Ag 引发的 CD4+ T 细胞产生高水平的 IL-4 (300-4000 pg/ml)。相比之下，SAC 诱导产生的 IL-4 水平非常低（<100 pg/ml），但 IFN-γ 的最大水平比 Ag 特异性 B 细胞高得多。通过阻断 CD40-CD40 配体 (CD40L) 相互作用或添加少量 rIL-12，Ag 特异性 B 细胞对 IL-4 合成的诱导显着减少。这些结果表明，由于 T 细胞上的 CD40L 与 CD40 相互作用，被同源 Ag 激活的 B 细胞优先诱导 IL-4 合成，而 SAC 优先诱导 T 细胞合成 IFN-γ，因为它们产生更多的 IL-12，并且触发 T 细胞上的 CD40L 的能力有限。
The role of Ag presentation by B cells in regulating the development of T cells with restricted cytokine profiles remains controversial. In this report, we compared Ag presentation by naive polyclonal B cells, naive Ag-specific B cells (from Ig receptor transgenic mice), or splenic adherent cells (SAC) and examined the capacity of these cells to influence cytokine production by CD4+ T cells. Freshly isolated naive B cells stimulated vigorous T cell proliferation and very strong T cell cytokine responses, but only when cultured with Ag recognized by the B cell Ig receptor (cognate Ag) and not when cultured with a noncognate Ag. Under these conditions, B cells activated by Ig receptor-mediated endocytosis of Ag induced both naive and Ag-primed CD4+ T cells to produce high levels of IL-4 (300-4000 pg/ml). In contrast, SAC induced the production of very low levels of IL-4 (<100 pg/ml) but much higher maximal levels of IFN-gamma than did Ag-specific B cells. The induction of IL-4 synthesis by Ag-specific B cells was significantly reduced by blocking CD40-CD40 ligand (CD40L) interactions or by the addition of small quantities of rIL-12. These results suggest that B cells activated by their cognate Ag preferentially induce IL-4 synthesis as a result of the interaction of CD40L on T cells with CD40, whereas SAC preferentially induce IFN-gamma synthesis by T cells as a result of their greater production of IL-12 and their limited capacity to trigger CD40L on T cells.