CD4+ T Cells Promote Antibody Production but Not Sustained Affinity Maturation during Borrelia burgdorferi Infection
CD4+ T Cells Promote Antibody Production but Not Sustained Affinity Maturation during Borrelia burgdorferi Infection
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DOI：
10.1128/iai.02471-14
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发表时间：
2015-01-01
影响因子：
3.1
通讯作者：
Baumgarth, Nicole
中科院分区：
文献类型：
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作者：
Elsner, Rebecca A.;Hastey, Christine J.;Baumgarth, Nicole
CD4T细胞对增强B细胞介导的免疫至关重要，支持诱导高亲和力、类别转换的抗体反应、长寿的浆细胞和记忆B细胞。以前的研究表明，伯氏疏螺旋体的免疫反应似乎缺乏强大的T依赖的B细胞反应，因为感染后几个月既没有形成长寿命的浆细胞，也没有形成记忆B细胞，而且在这种慢性病期间不断产生非转换性的IgM抗体。这些数据促使我们评估伯氏杆菌感染诱导的CD4T-FH细胞的诱导和功能。我们报道了伯氏杆菌感染后，CD4T细胞被有效地激发，T-FH细胞被诱导。这些CD4T细胞有助于控制伯氏杆菌的载量，并支持诱导伯氏杆菌特异性的免疫球蛋白G反应。然而，虽然针对典型的T依赖伯氏杆菌蛋白-关节炎相关蛋白(Arp)的抗体亲和力成熟是开始的，但这些增加后来被逆转，与之前观察到的生发中心退化一致。亲和力成熟的停止不是由于抑制或耗尽的CD4T细胞的出现，也不是由于调节性T细胞的强烈诱导。体外T-B共培养显示，从感染伯氏杆菌而不是伯氏杆菌免疫的小鼠分离的T细胞支持B细胞快速分化为分泌抗体的浆细胞，而不是持续增殖，反映了体内快速短期而不是长期T依赖的抗体反应的诱导。数据进一步表明，伯氏杆菌感染使体液反应从保护性、高亲和力和长寿的抗体反应转向快速诱导强诱导的、有限效力的短命抗体。
CD4 T cells are crucial for enhancing B cell-mediated immunity, supporting the induction of high-affinity, class-switched antibody responses, long-lived plasma cells, and memory B cells. Previous studies showed that the immune response to Borrelia burgdorferi appears to lack robust T-dependent B cell responses, as neither long-lived plasma cells nor memory B cells form for months after infection, and nonswitched IgM antibodies are produced continuously during this chronic disease. These data prompted us to evaluate the induction and functionality of B. burgdorferi infection-induced CD4 T-FH cells. We report that CD4 T cells were effectively primed and T-FH cells induced after B. burgdorferi infection. These CD4 T cells contributed to the control of B. burgdorferi burden and supported the induction of B. burgdorferi-specific IgG responses. However, while affinity maturation of antibodies against a prototypic T-dependent B. burgdorferi protein, Arthritis-related protein (Arp), were initiated, these increases were reversed later, coinciding with the previously observed involution of germinal centers. The cessation of affinity maturation was not due to the appearance of inhibitory or exhausted CD4 T cells or a strong induction of regulatory T cells. In vitro T-B cocultures demonstrated that T cells isolated from B. burgdorferi-infected but not B. burgdorferi-immunized mice supported the rapid differentiation of B cells into antibody-secreting plasma cells rather than continued proliferation, mirroring the induction of rapid short-lived instead of long-lived T-dependent antibody responses in vivo. The data further suggest that B. burgdorferi infection drives the humoral response away from protective, high-affinity, and long-lived antibody responses and toward the rapid induction of strongly induced, short-lived antibodies of limited efficacy.