Chudakov Dmitrii Borisovich, Kotsareva Olga Dmitrievna, Konovalova Maryia Vladimirovna, Tsaregorodtseva Daria Sergeevna, Shevchenko Marina Alexandrovna, Sergeev Anton Andreevich, Fattakhova Gulnar Vaisovna
Laboratory of Cell Interactions, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya St., 117997 Moscow, Russia.
Faculty of Medical Biology, Sechenov First Moscow State Medical University, 2 Bolshaya Pirogovskaya St., 1194535 Moscow, Russia.
Vaccines (Basel). 2022 Jun 17;10(6):969. doi: 10.3390/vaccines10060969.
Despite its paramount importance, the predominant association of early IgE production with harmless antigens, via germinal-center B- and T-cell subpopulations or extrafollicular activation, remains unresolved. The aim of this work was to clarify whether the reinforced IgE production following the subcutaneous immunization of BALB/c mice with low antigen doses in withers adipose tissue might be linked with intensified extrafollicular or germinal-center responses. The mice were immunized three times a week for 4 weeks in the withers region, which is enriched in subcutaneous fat and tissue-associated B cells, with high and low OVA doses and via the intraperitoneal route for comparison. During long-term immunization with both low and high antigen doses in the withers region, but not via the intraperitoneal route, we observed a significant accumulation of B220-CD1d-CD5-CD19+ B-2 extrafollicular plasmablasts in the subcutaneous fat and regional lymph nodes but not in the intraperitoneal fat. Only low antigen doses induced a significant accumulation of CXCR4+ CXCR5- CD4+ extrafollicular T helpers in the withers adipose tissue but not in the regional lymph nodes or abdominal fat. Only in subcutaneous fat was there a combination of extrafollicular helper accumulation. In conclusion, extrafollicular B- and T-cell activation are necessary for early IgE class switching.
尽管其至关重要，但早期IgE产生通过生发中心B细胞和T细胞亚群或滤泡外激活与无害抗原的主要关联仍未得到解决。这项工作的目的是阐明在用低剂量抗原皮下免疫BALB/c小鼠时，在肩胛间脂肪组织中增强的IgE产生是否可能与滤泡外或生发中心反应的增强有关。小鼠每周在富含皮下脂肪和组织相关B细胞的肩胛间区域进行三次免疫，持续4周，分别给予高剂量和低剂量的卵清蛋白（OVA），并通过腹腔注射途径作为对照。在肩胛间区域用低剂量和高剂量抗原进行长期免疫期间，但不是通过腹腔注射途径，我们观察到皮下脂肪和区域淋巴结中B220-CD1d-CD5-CD19+B-2滤泡外浆母细胞显著积累，而腹腔脂肪中没有。只有低剂量抗原诱导肩胛间脂肪组织中CXCR4+CXCR5-CD4+滤泡外辅助性T细胞显著积累，而区域淋巴结或腹部脂肪中没有。只有在皮下脂肪中存在滤泡外辅助细胞积累的组合。总之，滤泡外B细胞和T细胞激活是早期IgE类别转换所必需的。
