粘膜免疫系における記憶B細胞の選択機構

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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.