Identification of cells and molecules involving in the production of cedar pollen-specific IgE

• Project/Area Number: 21791652
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Otorhinolaryngology
• Research Institution: Osaka Medical College
• Principal Investigator: KANAZAWA Atsuko Osaka Medical College, 医学部, 非常勤医師 (10531379)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 鼻科学 / スギ花粉 / 花粉症 / 抗原非特異的IgE / 抗原特異的IgE / 顎下リンパ節 / 鼻咽頭関連リンパ組織

Research Abstract

The production of allergen-specific IgE in allergen-sensitized patients or animals has a mutual relation with the immunologic response leading to allergic rhinitis. We recently reported that after an intranasal (i.n.) injection of cedar pollen into mice, an IL-4-dependent increase in serum nonspecific IgE was a prerequisite for the production of serum allergen-specific IgE and that the submandibular lymph nodes were the main organ responsive to the i.n. injected allergen. After i.n. treatment with allergen (for IgE production) or allergen and complete Freund's adjuvant (for IgG production), we separated submandibular lymph node cells into macrophage (M)-and lymphocyte (L)-rich populations by discontinuous Percoll density-gradient centrifugation. Unexpectedly, bulk cells, but not the L-or M-rich population, produced significant amounts of IL-4, IgE, and IgG ; whereas the production was restored by the addition of Mac-1^+ cells in the M-rich fraction to the L-rich fraction. These results indicate that macrophages in the submandibular lymph nodes are essential not only for IL-4 or nonspecific Ig production but also for the class switching of Ig in lymphocytes in the initiation of allergic rhinitis.
The number of IgE^+ cells in the lymphoid tissues did not change significantly after an i.n., i.p., i.v. or s.c. injection of allergen into the mice, whereas a 2nd (s.c.) injection of the allergen into the i.v., but not into the i.n., i.p. or s.c., sensitized mice induced a small number of IgE^+/IgM^+/B220^+ B cells in the spleen. In contrast, the IgE+ cells were not seen in the blood or spleen of IL-4-/- mice after sensitization with the allergen. These results suggest that IgE+ basophils in the peripheral blood and IgE^+ B cells in the spleen might be IL-4-dependently induced as an indicator of sensitization with allergen and a precursor of cells secreting allergen-specific IgE antibody, respectively.

Research Products

• [Presentation] Macrophages regulate Ig class switching in B cells by controlling IL-4 production in T cells. (2011)
  • Author(s): Wakako Miyachi, Masayo Hirano, Hiromi Ogita-Nakanishi, Miku Arai, Junko Tashiro-Yamaji, Ryotaro Yoshida, Ryuji Kato, Yoshio Ijiri, Kazuhiko Tanaka, Atsuko Kanazawa, Ryo Kawata, Hiroshi Takenaka, Takahiro Kubota
  • Organizer: 第88回日本生理学会
  • Place of Presentation: (震災により中止、誌上発表)
  • Year and Date: 2011-03-30
• [Presentation] Essential role of macrophages in the initiation of allergic rhinitis : Regulation of class switching of nonspecific Ig in B cells by controlling IL-4 production in T cells of submandibular lymph nodes from mice sensitized intranasally(i.n.) once with cedar pollen (2010)
  • Author(s): Masayo Hirano, Hiromi Ogita-Nakanishi, Miku Arai, Junko Tashiro-Yamaji, Yumiko Yamamoto-Kimoto, Kanji Sakurai, Masako Miyoshi-Higashino, Yoshihiro Inoue, Ryuji Kato, Yoshio Ijiri, Kazuhiko Tanaka, Atsuko Kanazawa, Takahiro Kubota, Hiroshi Takenaka, Ryotaro Yoshida.
  • Organizer: 14^<th> International Congress og Immunology
  • Place of Presentation: Kobe
  • Year and Date: 2010-08-25
• [Presentation] Essential role of macrophages in the initiation of allergic rhinitis : Regulation of class switching of nonspecific Ig… (2010)
  • Author(s): Hirano M, et al.
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-25
• [Presentation] Macrophages regulate Ig class switching in B cells by controlling IL-4 production in T cells (2010)
  • Author(s): Miyachi W, et al.
  • Organizer: 第88回日本生理学会
  • Place of Presentation: (震災により中止;誌上発表)
  • Year and Date: 2010-03-30
• [Presentation] Role of macrophages in the initiation of allergic rhinitis : Regulation of the class of Ig to be produced in B cells by controlling IL-4 production in T cells of mouse submandibular lymph node (2009)
  • Author(s): Masayo Hirano, Hiromi Ogita-Nakanishi, Junko Tashiro-Yamaji, Yoshihiro Inoue, Ryuji Kato, Yoshio Ijiri, Kazuhiko Tanaka, Atsuko Kanazawa, Takahiro Kubota, Hiroshi Takenaka, Ryotaro Yoshida.
  • Organizer: 第38回日本免疫学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-04
• [Presentation] Role of macrophages in the initiation of allergic rhinitis : Regulation.... (2009)
  • Author(s): Hirano M., et al.
  • Organizer: 日本免疫学会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2009-12-04
• [Presentation] Essential role of macrophages in the in vitro production of IL-4 or nonspecific IgE or IgG antibody by lymphocytes of submandibular lymph node from mice sensitized intranasally once with cedar pollen (2009)
  • Author(s): Masayo Hirano, Hiromi Ogita-Nakanishi, Junko Tashiro-Yamaji, Yumiko Kimoto-Yamamoto, Kanji Sakurai, Masako Miyoshi-Higashino, Ryuji Kato, Yoshio Ijiri, Kazuhiko Tanaka, Atsuko Kanazawa, Hiroshi Takenaka, Takahiro Kubota, Ryotaro Yoshida.
  • Organizer: 第17回マクロファージ分子細胞生物学シンポジウム
  • Place of Presentation: 金沢
  • Year and Date: 2009-07-03
• [Presentation] Essential role of macrophages in the in vitro production of IL-4 or.... (2009)
  • Author(s): Hirano M., et al.
  • Organizer: 17^<th> International Symposium on Molecular Cell Biology of Macrophages
  • Place of Presentation: KKRホテル金沢(金沢)
  • Year and Date: 2009-07-03
• [Presentation] スギ花粉抗原投与によるIgE 産生機構-末梢血および脾臓のIgE 陽性細胞について- (2009)
  • Author(s): 東野昌子, 平野雅予, 中西仁美, 紀本有実子, 桜井幹士, 金沢敦子, 山路純子, 吉田龍太郎, 竹中洋
  • Organizer: 第110回日本耳鼻咽喉科学会
  • Place of Presentation: 東京
  • Year and Date: 2009-05-16
• [Presentation] スギ花粉抗原投与によるIgE産生機構―末梢血および脾臓のIgE陽性細胞.... (2009)
  • Author(s): 東野昌子, ら
  • Organizer: 日本耳鼻咽喉科学会
  • Place of Presentation: ザ・プリンスパークタワー東京(東京)
  • Year and Date: 2009-05-14
• [Remarks] ホームページ等
  • URL: http://www.osaka-med.ac.jp/deps/oto2/html/kenkyu/theme.html