Nowocin Anna K, Meader Lucy, Brown Kathryn, Elgueta Raul, Wong Wilson
From the MRC Centre for Transplantation, King's College London School of Medicine at Guy's, King's and St. Thomas' Hospitals, London, United Kingdom.
Exp Clin Transplant. 2019 Jun;17(3):330-338. doi: 10.6002/ect.2017.0261. Epub 2019 Mar 14.
Tertiary lymphoid organs are formed at sites of chronic inflammation and are thought to contribute to the immune response. Here, we aimed to characterize the structure and function of tertiary lymphoid organs in a model of murine kidney allotransplant to understand their role in alloimmunity.
We transplanted 4 C57BL/6 mouse kidneys (isograft group) and 17 DBA/2 mouse kidneys into C57BL/6 mouse recipients. Three DBA/2-to-C57BL/6 transplant mice that rejected their grafts acutely (before 10 days posttransplant) were excluded from the study. The 14 surviving DAB2 grafts were retrieved at day 45 posttransplant and evaluated histologically. The presence of antibody-secreting cells and circulating levels of donor-specific antibodies were also evaluated.
We found that tertiary lymphoid organs can be associated with a beneficial response in a kidney allotransplant model. Characterization of B-cell subsets within tertiary lymphoid organs in mouse kidney allografts revealed naive, plasma, and memory B cells, which were mostly grouped within or in close proximity of tertiary lymphoid organs. Staining for intracellular immunoglobulin G showed that many of the B cells within tertiary lymphoid organs were capable of producing antibodies. Although allospecific antibodies were found in the serum of recipient mice and were deposited in the transplanted kidneys, graft function was not affected in this model.
B cells within tertiary lymphoid organs are functional and contribute to the humoral arm of the alloresponse. However, tertiary lymphoid organs are not necessarily associated with graft rejection, suggesting that protective mechanisms are at play.
三级淋巴器官在慢性炎症部位形成，被认为有助于免疫反应。在此，我们旨在表征小鼠肾同种异体移植模型中三级淋巴器官的结构和功能，以了解它们在同种免疫中的作用。
我们将4个C57BL/6小鼠肾脏（同基因移植组）和17个DBA/2小鼠肾脏移植到C57BL/6小鼠受体中。3只急性排斥移植物（移植后10天内）的DBA/2至C57BL/6移植小鼠被排除在研究之外。在移植后第45天取出14个存活的DAB2移植物并进行组织学评估。还评估了抗体分泌细胞的存在和供体特异性抗体的循环水平。
我们发现在肾同种异体移植模型中，三级淋巴器官可能与有益反应相关。对小鼠肾同种异体移植中三级淋巴器官内B细胞亚群的表征显示，有幼稚B细胞、浆细胞和记忆B细胞，它们大多聚集在三级淋巴器官内或其附近。细胞内免疫球蛋白G染色显示，三级淋巴器官内的许多B细胞能够产生抗体。尽管在受体小鼠血清中发现了同种特异性抗体并沉积在移植肾脏中，但在该模型中移植物功能未受影响。
三级淋巴器官内的B细胞具有功能，有助于同种异体反应的体液免疫部分。然而，三级淋巴器官不一定与移植物排斥相关，这表明存在保护机制。
