Macaulay A E, DeKruyff R H, Goodnow C C, Umetsu D T
Department of Pediatrics, Stanford University, CA 94305, USA.
J Immunol. 1997 May 1;158(9):4171-9.
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.
B细胞提呈抗原在调节具有受限细胞因子谱的T细胞发育中的作用仍存在争议。在本报告中，我们比较了天然多克隆B细胞、天然抗原特异性B细胞（来自Ig受体转基因小鼠）或脾黏附细胞（SAC）的抗原提呈情况，并检测了这些细胞影响CD4⁺T细胞产生细胞因子的能力。新鲜分离的天然B细胞可刺激强烈的T细胞增殖和非常强烈的T细胞细胞因子反应，但仅在与B细胞Ig受体识别的抗原（同源抗原）一起培养时才会出现这种情况，与非同源抗原一起培养时则不会。在这些条件下，通过Ig受体介导的抗原内吞作用激活的B细胞可诱导天然和抗原致敏的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的最大水平比抗原特异性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，可显著降低抗原特异性B细胞对IL-4合成的诱导。这些结果表明，同源抗原激活的B细胞由于T细胞上的CD40L与CD40相互作用而优先诱导IL-4合成，而SAC由于其IL-12产量更高且触发T细胞上CD40L的能力有限，优先诱导T细胞合成IFN-γ。
