Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
Department of Anesthesiology, China-Japan Friendship Hospital, Beijing, China.
Int Immunopharmacol. 2021 Feb;91:107337. doi: 10.1016/j.intimp.2020.107337. Epub 2021 Jan 2.
CD40 ligand (CD40L) and B-cell activating factor (BAFF) play important roles in the function of B cells. However, the difference of their regulatory effects remains obscure. In this study, we used anti-CD40 to imitate CD40L and investigated the different regulatory effects of CD40L and BAFF on the function of B cells. In the functional analyses, both anti-CD40 and BAFF significantly enhanced the survival and differentiation of B cells, and slightly increased the activation and proliferation. However, in the transcriptome analysis, anti-CD40 and BAFF exerted very different regulation on the gene expression profile of B cells. Anti-CD40 upregulated the expression of genes related to the adaptive immune function of B cells, but BAFF enhanced the genes associated with the innate immune function. Furthermore, the effect analysis of the combination of anti-CD40 or BAFF with anti-IgM also demonstrated that anti-CD40 could cooperate with anti-IgM to promote the proliferation of B cells, but BAFF could not do it. The mechanism study revealed that the different effects of anti-CD40 and BAFF on B cells were resulting from the different modulation on NF-кB, ERK1/2, and PI3K-AKT signaling pathways. Collectively, the results suggest that CD40L mainly promotes adaptive immune function of B cells, but BAFF primarily enhances innate immune function.
CD40 配体（CD40L）和 B 细胞激活因子（BAFF）在 B 细胞的功能中发挥重要作用。然而，它们的调节作用的差异仍然不清楚。在这项研究中，我们使用抗 CD40 来模拟 CD40L，并研究了 CD40L 和 BAFF 对 B 细胞功能的不同调节作用。在功能分析中，抗 CD40 和 BAFF 均显著增强了 B 细胞的存活和分化，并略微增加了激活和增殖。然而，在转录组分析中，抗 CD40 和 BAFF 对 B 细胞的基因表达谱产生了非常不同的调节作用。抗 CD40 上调了与 B 细胞适应性免疫功能相关的基因表达，但 BAFF 增强了与固有免疫功能相关的基因。此外，抗 CD40 或 BAFF 与抗 IgM 联合的效果分析也表明，抗 CD40 可以与抗 IgM 协同促进 B 细胞增殖，但 BAFF 不能。机制研究表明，抗 CD40 和 BAFF 对 B 细胞的不同作用是由于它们对 NF-кB、ERK1/2 和 PI3K-AKT 信号通路的不同调节所致。综上所述，结果表明 CD40L 主要促进 B 细胞的适应性免疫功能，而 BAFF 主要增强固有免疫功能。
