Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Front Immunol. 2020 Sep 29;11:571321. doi: 10.3389/fimmu.2020.571321. eCollection 2020.
Humoral immunity is established after differentiation of antigen-specific B cells into plasma cells (PCs) that produce antibodies of relevant specificities. Defects in the development, activation, or differentiation of B cells severely compromises the immune response. Primary immunodeficiencies are often characterized by hypogammaglobulinemia and the inability to mount effective antigen-specific antibody responses, resulting in increased susceptibility to infections. After IgA deficiency, which is most often asymptomatic, common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency, but in most cases the underlying genetic causes are unknown or their roles in disease pathogenesis are poorly understood. In this study, we developed a protocol for stimulation of primary human B cells for subsequent analyses of PC differentiation and antibody production. With this approach, we were able to detect a population of CD38 IRF4 Blimp-1 cells committed to PC fate and IgG production, including when starting from cryopreserved samples. The application of functional assays to characterize PC differentiation and possible defects therein in B cells from patients suffering from primary antibody deficiencies with late B cell defects could increase our understanding of the disease pathophysiology and underlying mechanisms.
体液免疫是在抗原特异性 B 细胞分化为浆细胞 (PCs) 后建立的，浆细胞产生具有相关特异性的抗体。B 细胞的发育、激活或分化缺陷严重损害免疫反应。原发性免疫缺陷症常表现为低丙种球蛋白血症和无法产生有效的抗原特异性抗体反应，从而导致易感染。在最常见无症状的 IgA 缺陷之后，常见可变免疫缺陷症 (CVID) 是最常见的有症状原发性免疫缺陷症，但在大多数情况下，其潜在的遗传原因尚不清楚，或其在疾病发病机制中的作用仍知之甚少。在这项研究中，我们开发了一种刺激原代人 B 细胞的方案，用于随后分析 PC 分化和抗体产生。通过这种方法，我们能够检测到一群 CD38 IRF4 Blimp-1 细胞，这些细胞注定要成为 PC，并产生 IgG，包括从冷冻保存的样本开始。应用功能测定法来表征患有晚期 B 细胞缺陷的原发性抗体缺陷症患者的 B 细胞中的 PC 分化和可能的缺陷，可能会增加我们对疾病病理生理学和潜在机制的理解。
