4.7 Article

Different regulatory effects of CD40 ligand and B-cell activating factor on the function of B cells

Journal

INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 91, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.intimp.2020.107337

Keywords

CD40 ligand; B-cell activating factor; Different regulatory effects; B cells

Funding

  1. National Natural Science Foundation of China, China [81603361]

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The study showed that CD40L primarily promotes the adaptive immune function of B cells, while BAFF mainly enhances the innate immune function. The differences in regulatory effects were attributed to the modulation of NF-kappa B, ERK1/2, and PI3K-AKT signaling pathways by anti-CD40 and BAFF.
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-kappa B, 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.

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