Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of RAS, 117997, 16/10 Miklukho-Maklaya Street, Moscow, Russia.
Sechenov First Moscow State Medical University, 127994, 4 Rachmanov Alley, Moscow, Russia.
BMC Immunol. 2020 Aug 7;21(1):45. doi: 10.1186/s12865-020-00376-7.
Numerous data obtained by different research laboratories indicate that specific IgE production is triggered independently of specific IgG or IgA ones and so it is not linked to fully matured germinal centers formation in the secondary lymphoid organs. The aim of this study was to clarify whether specific IgE production is triggered by low antigen doses administrated in tertiary tissues enriched by lymphoid structures.
Ovalbumin (OVA) in different doses (100 ng to 10 μg) was administrated three times a week for 4-5 weeks intraperitoneally (i.p.) or subcutaneously (s.c.) to female BALB/c mice in the wither region which is enriched in fat-associated lymphoid clusters or in the foot pad region not containing them.
OVA-specific IgE was predominantly induced by low but not high antigen doses and only after immunization into the withers. IgE isotype switching was triggered exclusively in the withers adipose tissue but not in the regional lymph nodes while mature IgE expressing cells were observed both in the withers and lymph nodes. Anti-proliferative genotoxic stress inducing drugs shifted the balance from IgG1 towards IgE production.
Tertiary lymphoid structures possess unique environment where B-cell antibody isotype switching to IgE predominantly occurs. This phenomenon is partially explained by hampered proliferation of B-cells in these structures.
不同研究实验室获得的大量数据表明，特异性 IgE 的产生是独立于特异性 IgG 或 IgA 产生的，因此与次级淋巴器官中完全成熟的生发中心形成无关。本研究旨在阐明特异性 IgE 的产生是否是由富含淋巴结构的三级组织中低剂量抗原引发的。
将卵清蛋白 (OVA) 以不同剂量（100ng 至 10μg）每周三次经腹膜内 (i.p.) 或皮下 (s.c.) 注射到雌性 BALB/c 小鼠的肩胛区域或不包含它们的脚掌区域，持续 4-5 周。
OVA 特异性 IgE 主要由低剂量而不是高剂量的抗原诱导，并且仅在肩胛部位免疫时才会诱导。IgE 同种型转换仅在肩胛脂肪组织中触发，而不在区域淋巴结中触发，而成熟的 IgE 表达细胞在肩胛和淋巴结中均观察到。抗增殖遗传毒性应激诱导药物将 IgG1 向 IgE 产生的平衡转移。
三级淋巴结构具有独特的环境，其中 B 细胞抗体同种型转换为 IgE 主要发生在此环境中。这种现象部分可以解释为这些结构中 B 细胞增殖受阻。
