粘膜免疫系における記憶B細胞の選択機構

粘蛋白免疫球蛋白（IG）A优势已被认为与伊加重链恒定区的优先类别转换重组（CSR）相关。为了研究粘膜免疫系统中的B细胞应答和选择，我们监测了鼻相关淋巴组织（NALT）中的抗NP应答，NALT是上呼吸道和口腔的主要诱导部位。结果表明，偶联于鸡球蛋白的半抗原（4-羟基-3-硝基苯基）乙酰（NP）刺激NALT后，B细胞活化，引起以高亲和力伊加抗体为主的二次抗NP反应。然而，在细胞水平上，NP-特异性IgG^+ B细胞扩增并维持其数量，作为生殖中心（GC）的主要群体，支持了IgG重链恒定区的CSR在NALT中有效运作的观点。IgG^+和伊加^+ GC B细胞都在V_H基因V186.2处积累了体细胞突变，表明亲和力成熟，这表明IgG^+和伊加^+细胞在GC中被抗原同等地选择。相反，高亲和力IgG^+/NP特异性B细胞在记忆区几乎检测不到，而这些细胞在伊加记忆区占主导地位。这些结果支持这样的观点，即NALT配备有独特的机制，提供IgA特异性富集高亲和力细胞进入记忆隔室。

Mucosal immunoglobulin (Ig) A dominance has been proposed to be associated with preferential class switch recombination (CSR) to the IgA heavy chain constant region. To investigate B cell response and selection in mucosal immune system, we monitored anti-NP response in Nasal-associated lymphoid tissue (NALT), which is the major inductive site for the upper respiratory tract and oral cavity. The results showed that B cell activation in NALT upon stimulation with the hapten (4-hydroxy-3-nitrophenyl) acetyl (NP) coupled to chicken globulin caused the secondary anti-NP response dominated by IgA antibodies with high affinity. On the cellular level, 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 operated efficiently in NALT. Both IgG^+ and IgA^+ GC B cells accumulated somatic mutations in the V_H gene, V186.2, indicative of affinity maturation, suggesting that IgG^+ and IgA^+ cells were equally selected by antigen in GCs. In contrast, high affinity IgG^+/NP-specific B cells were barely detected in the memory compartment, whereas such cells dominated the IgA memory compartment. These results support the view that NALT is equipped with a unique machinery providing IgA-specific enrichment of high affinity cells into the memory compartment.