Mucosal Immunobiology and Vaccine Research Center and the Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, S-405-30 Gothenburg, Sweden.
Department of Clinical Immunology and Transfusion Medicine, Sahlgrenska University Hospital, S-405-30 Gothenburg, Sweden.
Nat Commun. 2016 Sep 6;7:12698. doi: 10.1038/ncomms12698.
Understanding how memory B cells are induced and relate to long-lived plasma cells is important for vaccine development. Immunity to oral vaccines has been considered short-lived because of a poor ability to develop IgA B-cell memory. Here we demonstrate that long-lived mucosal IgA memory is readily achieved by oral but not systemic immunization in mouse models with NP hapten conjugated with cholera toxin and transfer of B1-8(high)/GFP(+) NP-specific B cells. Unexpectedly, memory B cells are poorly related to long-lived plasma cells and less affinity-matured. They are α4β7-integrin(+)CD73(+)PD-L2(+)CD80(+) and at systemic sites mostly IgM(+), while 80% are IgA(+) in Peyer's patches. On reactivation, most memory B cells in Peyer's patches are GL7(-), but expand in germinal centres and acquire higher affinity and more mutations, demonstrating strong clonal selection. CCR9 expression is found only in Peyer's patches and appears critical for gut homing. Thus, gut mucosal memory possesses unique features not seen after systemic immunization.
了解记忆 B 细胞如何被诱导以及与长寿浆细胞的关系对于疫苗的开发非常重要。由于口服疫苗诱导 IgA 记忆 B 细胞的能力较差，因此其免疫作用被认为是短暂的。在这里，我们通过用霍乱毒素偶联 NP 半抗原并转移 NP 特异性 B1-8(high)/GFP(+)B 细胞的方法，在具有 NP 表位的小鼠模型中证实，口服而非全身免疫可轻易地产生长寿黏膜 IgA 记忆。出乎意料的是，记忆 B 细胞与长寿浆细胞的相关性较差，亲和力成熟程度较低。它们是 α4β7 整合素(+)CD73(+)PD-L2(+)CD80(+)，在全身部位主要是 IgM(+)，而在派尔氏结中 80%是 IgA(+)。在再激活时，派尔氏结中的大多数记忆 B 细胞是 GL7(-)，但在生发中心中扩增并获得更高的亲和力和更多的突变，表明强烈的克隆选择。CCR9 表达仅在派尔氏结中发现，对肠道归巢似乎至关重要。因此，肠道黏膜记忆具有全身免疫后未见的独特特征。
