Macrophage migration inhibitory factor (MIF) is a chemokine-like inflammatory cytokine, which plays a pivotal role in the pathogenesis of inflammatory and cardiovascular diseases as well as cancer. We previously identified MIF as a novel B cell chemokine that promotes B cell migration through non-cognate interaction with the CXC chemokine receptor CXCR4 and CD74, the surface form of MHC class II invariant chain. In this study, we have analyzed the regulation of the MIF receptors under inflammatory conditions by investigating the impact of lipopolysaccharide (LPS), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) on CD74 and CXCR4 expression in B lymphocytes. We found that both LPS and TNF-α stimulation of primary B cells and the human B myeloma cell line RPMI-8226 enhanced protein expression as well as mRNA levels of CD74 in a time- and dose-dependent manner. By contrast, no effect on CXCR4 expression was observed. Selective inhibition of IκBα phosphorylation significantly attenuated LPS-induced expression of CD74, suggesting the contribution of NF-κB signaling pathways to the regulation of CD74 expression. Importantly, individual or simultaneous blockade of MIF or CD74 using specific neutralizing antibodies markedly affected B cell proliferation after LPS exposure. Taken together, our findings unveil a connection between the pro-proliferative activity of MIF/CD74 signaling in B cells and inflammation, offering novel target mechanisms in inflammatory cardiovascular or autoimmune pathogenesis.

巨噬细胞迁移抑制因子（MIF）是一种趋化因子样的炎症细胞因子，在炎症和心血管疾病以及癌症的发病机理中起着关键作用。我们先前将MIF确定为一种新型B细胞趋化因子，它通过与CXC趋化因子受体CXCR4和CD74（MHC II类不变链的表面形式）的非同源相互作用来促进B细胞迁移。在这项研究中，我们通过研究脂多糖（LPS），肿瘤坏死因子-α（TNF-α）和白介素-1β（IL-1β）对CD74和CXCR4表达的影响，分析了炎症条件下MIF受体的调节。在B淋巴细胞中。我们发现，LPS和TNF-α对原代B细胞和人B骨髓瘤细胞系RPMI-8226的刺激均以时间和剂量依赖性方式增强了CD74的蛋白表达和mRNA水平。相反，未观察到对CXCR4表达的影响。IκBα磷酸化的选择性抑制显着减弱了LPS诱导的CD74表达，提示NF-κB信号通路对CD74表达的调节有贡献。重要的是，使用LPS暴露后，使用特异性中和抗体对MIF或CD74的单独或同时阻断显着影响了B细胞的增殖。综上所述，我们的发现揭示了B细胞中MIF / CD74信号传导的增殖活性与炎症之间的联系，为炎症性心血管或自身免疫性发病机制提供了新的靶标机制。