Mesh : Mice Animals B-Lymphocytes Lymphoid Tissue Spleen / metabolism Signal Transduction CD55 Antigens / metabolism Erythrocytes

来  源:   DOI:10.1038/s41590-023-01690-z   PDF(Pubmed)

Abstract:
Spleen marginal zone (MZ) B cells are important for antibody responses against blood-borne antigens. The signals they use to detect exposure to blood are not well defined. Here, using intravital two-photon microscopy in mice, we observe transient contacts between MZ B cells and red blood cells that are in flow. We show that MZ B cells use adhesion G-protein-coupled receptor ADGRE5 (CD97) for retention in the spleen. CD97 function in MZ B cells depends on its ability to undergo autoproteolytic cleavage and signaling via Gα13 and ARHGEF1. Red blood cell expression of the CD97 ligand CD55 is required for MZ B cell homeostasis. Applying a pulling force on CD97-transfected cells using an optical C-trap and CD55+ beads leads to accumulation of active RhoA and membrane retraction. Finally, we show that CD97 deficiency leads to a reduced T cell-independent IgM response. Thus, our studies provide evidence that MZ B cells use mechanosensing to position in a manner that enhances antibody responses against blood-borne antigens.
摘要:
脾边缘区(MZ)B细胞对于针对血源性抗原的抗体反应很重要。他们用来检测血液暴露的信号没有很好的定义。这里,在小鼠体内使用活体双光子显微镜,我们观察到MZB细胞和流动的红细胞之间的短暂接触。我们显示MZB细胞使用粘附G蛋白偶联受体ADGRE5(CD97)保留在脾脏中。MZB细胞中的CD97功能取决于其通过Gα13和ARHGEF1进行自身蛋白水解切割和信号传导的能力。CD97配体CD55的红细胞表达是MZB细胞稳态所必需的。使用光学C陷阱和CD55+珠在CD97转染的细胞上施加拉力导致活性RhoA的积累和膜收缩。最后,我们显示CD97缺乏导致T细胞非依赖性IgM应答降低。因此,我们的研究提供了证据,证明MZB细胞利用机械传感定位,从而增强针对血源性抗原的抗体应答.
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