Division of Infectious Diseases, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Eur J Immunol. 2024 Aug;54(8):e2350736. doi: 10.1002/eji.202350736. Epub 2024 May 3.
CD11c, FcRL5, or T-bet are commonly expressed by B cells expanding during inflammation, where they can make up >30% of mature B cells. However, the association between the proteins and differentiation and function in the host response remains largely unclear. We have assessed the co-expression of CD11c, T-bet, and FcRL5 in an in vitro B-cell culture system to determine how stimulation via the BCR, toll-like receptor 9 (TLR9), and different cytokines influence CD11c, T-bet, and FcRL5 expression. We observed different expression dynamics for all markers, but a largely overlapping regulation of CD11c and FcRL5 in response to BCR and TLR9 activation, while T-bet was strongly dependent on IFN-γ signaling. Investigating plasma cell differentiation and APC functions, there was no association between marker expression and antibody secretion or T-cell help. Rather the functions were associated with TLR9-signalling and B-cell-derived IL-6 production, respectively. These results suggest that the expression of CD11c, FcRL5, and T-bet and plasma cell differentiation and improved APC functions occur in parallel and are regulated by similar activation signals, but they are not interdependent.
CD11c、FcRL5 或 T-bet 通常在炎症期间表达，此时它们可以占到成熟 B 细胞的>30%。然而，这些蛋白与宿主反应中的分化和功能之间的关联在很大程度上仍不清楚。我们评估了体外 B 细胞培养系统中 CD11c、T-bet 和 FcRL5 的共表达，以确定 BCR、Toll 样受体 9（TLR9）和不同细胞因子的刺激如何影响 CD11c、T-bet 和 FcRL5 的表达。我们观察到所有标志物的表达动力学都不同，但 BCR 和 TLR9 激活对 CD11c 和 FcRL5 的调控具有很大的重叠性，而 T-bet 则强烈依赖于 IFN-γ 信号。研究浆细胞分化和 APC 功能时，标志物表达与抗体分泌或 T 细胞辅助之间没有关联。相反，功能分别与 TLR9 信号和 B 细胞衍生的 IL-6 产生相关。这些结果表明，CD11c、FcRL5 和 T-bet 的表达以及浆细胞分化和增强的 APC 功能是平行发生的，并受到相似的激活信号的调控，但它们不是相互依赖的。
