| Project/Area Number |
11670332
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | NATIONAL INSTITUTE OF INFECTIOUS DISEASES |
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Principal Investigator |
TOSHITADA Takemori NATIONAL INSTITUTE OF INFECTIOUS DISEASES, Department of Immunology, Director (60114295)
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| Co-Investigator(Kenkyū-buntansha) |
TAMURA Shinichi NATIONAL INSTITUTE OF INFECTIOUS DISEASES, Department of Pathology, Chief (20100084)
TAKAHASHI Yoshimasa NATIONAL INSTITUTE OF INFECTIOUS DISEASES, Department of Immunology, Researcher (60311403)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | IgA antibodies / mucosal immunity / immunological memory / Nasal-associated lymphoid tissue / germinal center / class-switch / high-affinity / secondary response / IgA / 胚中心 / 高親和性抗体 / 胚中心B細胞 / IgG抗体 |
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| Research Abstract |
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.
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