Isotype-specific selection of high affinity memory B cells in nasal-associated lymphoid tissue.
Isotype-specific selection of high affinity memory B cells in nasal-associated lymphoid tissue.
复制标题
DOI：
10.1084/jem.194.11.1597
复制
发表时间：
2001-12-03
影响因子：
15.3
通讯作者：
Takemori, T
中科院分区：
文献类型：
--
作者：
Shimoda, M;Nakamura, T;Takahashi, Y;Asanuma, H;Tamura, S;Kurata, T;Mizuochi, T;Azuma, N;Kanno, C;Takemori, T
粘膜免疫球蛋白 (Ig)A 优势被认为与 IgA 重链恒定区 Cα 的优先类别转换重组 (CSR) 有关。在这里，我们报道了鼻相关淋巴组织（NALT）中的 B 细胞在受到与鸡 γ 球蛋白偶联的半抗原（4-羟基-3-硝基苯基）乙酰基（NP）刺激后引起了由高亲和力 IgA 抗体主导的抗 NP 记忆反应。然而，在反应中，NP 特异性 IgG+ B 细胞扩增并维持其数量，成为生发中心 (GC) 中的主要群体，这支持了 IgG 重链恒定区 Cγ 的 CSR 在 NALT 中有效运作的观点。 IgG+ 和 IgA+ GC B 细胞都积累了体细胞突变，表明亲和力成熟程度相似，表明两种类型的细胞均受到抗原的选择。尽管在 GC 中进行了选择，但在 IgG 记忆室中几乎检测不到高亲和力 NP 特异性 B 细胞，而此类细胞在 IgA 记忆室中占主导地位。结合GC和记忆B细胞中VH基因克隆型的分析，我们认为NALT配备了独特的机制，可将高亲和力细胞的IgA特异性富集到记忆室中，从而促进高亲和力和非炎性分泌抗体的免疫。
Mucosal immunoglobulin (Ig)A dominance has been proposed to be associated with preferential class switch recombination (CSR) to the IgA heavy chain constant region, Cα. Here, we report that B cell activation in nasal-associated lymphoid tissue (NALT) upon stimulation with the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP) coupled to chicken γ globulin caused an anti-NP memory response dominated by high affinity IgA antibodies. In the response, however, NP-specific IgG+ B cells expanded and sustained their number as a major population in germinal centers (GCs), supporting the view that CSR to IgG heavy chain constant region, Cγ, operated efficiently in NALT. Both IgG+ and IgA+ GC B cells accumulated somatic mutations, indicative of affinity maturation to a similar extent, suggesting that both types of cell were equally selected by antigen. Despite the selection in GCs, high affinity NP-specific B cells were barely detected in the IgG memory compartment, whereas such cells dominated the IgA memory compartment. Taken together with the analysis of the VH gene clonotype in GC and memory B cells, we propose that NALT is equipped with a unique machinery providing IgA-specific enrichment of high affinity cells into the memory compartment, facilitating immunity with high affinity and noninflammatory secretory antibodies.