In the intestine, IgA antibody-secreting B cells (IgA-ASCs) and helper T cells coordinate to maintain local homeostasis while their dysregulation could lead to development of intestinal inflammatory diseases. However, mechanisms underlying the coordinated localization and function of the B and T cells into the intestine, particularly the colon, are poorly understood. We herein report the first evidence that the gut-homing chemokine receptor CCR10⁺ IgA-ASCs form conjugates with helper T cells, preferentially regulatory T cells, at their differentiation sites of gut-associated lymphoid organs for their coordinated co-localization into the colon to promote local homeostasis. In CCR10-knockout mice, defective migration of IgA-ASCs also resulted in defective T-cell migration and homeostasis, and development of inflammatory symptoms in the colon. Antigen-specific interaction of CCR10⁺ IgA-ASCs and T cells is crucial for their homeostatic establishment in the colon. On the other hand, in IgA-knockout mice, preferential expansion of CCR10⁺ IgG1-ASCs with regulatory functions compensated for CCR10⁺ IgA-ASCs to help maintain colonic homeostasis. The preferential expansion of specific subclasses of CCR10⁺ IgG-ASCs with regulatory functions was also found in asymptomatic IgA-deficient patients. These findings suggest coordinated cell migration as a novel mechanism underlying localization and function of B and T cells in colonic homeostatic regulation.

在肠道中，分泌 IgA 抗体的 B 细胞 (IgA-ASCs) 和辅助性 T 细胞协调维持局部稳态，而它们的失调可能导致肠道炎症性疾病的发展。然而，人们对 B 细胞和 T 细胞在肠道（尤其是结肠）中协调定位和发挥功能的机制知之甚少。我们在此报告了肠道归巢趋化因子受体 CCR10 ^{+的第一个证据}IgA-ASC 在肠道相关淋巴器官的分化位点与辅助性 T 细胞（优先调节性 T 细胞）形成结合物，以协调共定位到结肠中以促进局部稳态。在 CCR10 敲除小鼠中，IgA-ASCs 的迁移缺陷也导致 T 细胞迁移和稳态缺陷，以及结肠炎症症状的发展。^{CCR10 +} IgA-ASC 和 T 细胞的抗原特异性相互作用对于它们在结肠中的稳态建立至关重要。另一方面，在 IgA 敲除小鼠中，具有调节功能的 CCR10 ⁺ IgG1-ASC 的优先扩增补偿了 CCR10 ⁺ IgA-ASC，以帮助维持结肠稳态。CCR10特定亚类的优先扩展⁺在无症状的 IgA 缺陷患者中也发现了具有调节功能的 IgG-ASC。这些发现表明，协调细胞迁移是 B 细胞和 T 细胞在结肠稳态调节中定位和发挥功能的一种新机制。