MTA-ELTE Immunology Research Group, Eötvös Loránd University, Budapest, Hungary.
Department of Immunology, Eötvös Loránd University, Budapest, Hungary.
Front Immunol. 2019 Jul 2;10:1493. doi: 10.3389/fimmu.2019.01493. eCollection 2019.
The complement system and Toll-like receptors (TLRs) are essential contributors of innate immunity. Separate activation of these systems has been shown to play a role in initiating and shaping the adaptive immune response, however the modulation of various B cell functions by the simultaneous involvement of these two systems has not yet been uncovered. We demonstrate here that occupancy of complement receptor type 1 (CR1, CD35) by its natural, complement component C3-derived ligand significantly and dose dependently reduces the TLR9-induced expression of activation markers, cytokine production, proliferation, and antibody production by human B cells, but has no effect on the TLR7-induced functions. The synergistic response to the simultaneous engagement of either TLR9 or TLR7 along with the BCR however, is significantly inhibited by CR1 occupancy. Our findings imply that both under physiological and pathological conditions, when complement- and TLR-activating microbial and damage products are present in the B cell environment, the cooperation between CR1 and TLR7 or TLR9 provides additional levels of the regulation of human B cell functions.
补体系统和 Toll 样受体（TLRs）是先天免疫的重要组成部分。已证实这些系统的单独激活在启动和塑造适应性免疫反应中发挥作用，然而，这两个系统的同时参与对各种 B 细胞功能的调节尚未被揭示。我们在这里证明，补体受体 1（CR1，CD35）被其天然的补体成分 C3 衍生配体占据，可显著且剂量依赖性地降低 TLR9 诱导的人类 B 细胞的活化标志物表达、细胞因子产生、增殖和抗体产生，但对 TLR7 诱导的功能没有影响。然而，当同时结合 TLR9 或 TLR7 以及 BCR 时，协同反应会被 CR1 占据显著抑制。我们的研究结果表明，无论是在生理还是病理条件下，当补体和 TLR 激活的微生物和损伤产物存在于 B 细胞环境中时，CR1 和 TLR7 或 TLR9 之间的合作提供了对人类 B 细胞功能的额外调节水平。
