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1998 Fiscal Year Final Research Report Summary

Studies on the regulatory mechanisms of V (D) J rearrangement using gene-inserted mice.

Research Project

Project/Area Number 08839005
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 免疫の制御機構
Research InstitutionThe University of Tokyo

Principal Investigator

TAKI Shinsuke  The University of Tokyo, Graduate School of Medicine, Department of Immunology, Lecturer, 大学院・医学系研究科, 講師 (50262027)

Project Period (FY) 1996 – 1998
Keywordsimmunoglogulin / gene rearrangement / allelic exclusion / B-cell development / interleukin-7 / transgenic mouse / gene targeting
Research Abstract

In order to understand the regulatory mechanisms of immunogoloulin heavy chain rearrangement, studies have been performed using a mutant mouse strain which carries a functionally rearranged V_H gene (V_HT15) inserted in the V_H locus on one chromosome (T15i/+ mice). I have shown followings. 1. In T15i/+ mice, B cells bearing the V_HT15 product occupies around 40% in the peripheral B cell compartment. In contrast, V_HT15^+B cells comply of around 80% of the B cell pool in T15i/+ mice carrying additional mutation in the IL-7 receptor loci (T15i/+IL-7R^<-/->), indicating that IL-7 is required for the survival of pro-B cells which undergo V(D)J rearrangement, so that in the absence of IL-7, pro-B cells cannot survive long enough to perform secondary rearrangements to disrupt the inserted V_H gene and generate functional V_H gene on the wild-type chromosome. 2. A kappa-chain transgene was additionally introduced into the T15i/+IL-7R^<-/-> mice. Even in these mice, the percentage of VHT15+B cells are still as high as that in non-transgenic T15i/+IL-7R^<-/-> mice. Moreover, the reduction of the B cell number due to the lack of IL-7 signals could not be restored by introducing both heavy and light cahins. These results indicate that the IL-7 signals function independently of surface Ig signals. 3. Secondary rearrangements on the mutant chromosome which destroy the inserted VH gene in T15i/+ mice might be due to the presence of the neomycin resistant cassette (neo) present upstream of the inserted VH gene which had been used as a selection marker in gene targeting. However, deletion of the ned gene using FLIP-FRT system did not alter the frequency of such secondary rearrangement. Thus, the secondary rearrangements occur as a result of the unique structure of VHT15 gene itself (for example, the sequence or the transcriptional activity of the accompanying promotor).

  • Research Products

    (4 results)

All Other

All Publications (4 results)

  • [Publications] Sonoda et al.: "B cell development under the condition of allelic inclusion." Immunity. 6. 225-233 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nagata et al.: "The Igα/Igβ heterodimer on μ-negative proB cells is component for transducing signals to induce early B cell differentiation." Immunity. 7. 559-570 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sonoda, E., Pewzner-Jung, Y., Schwers, S., Taki, S., Jung, S., Eilat, D.and Rajewsky, K.: "B cell development under the condition of allelic inclusion." Immunity. 6. 225-233 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagata, K., Nakamura, T., Kitamura, F., Kuramochi, S., Taki, S., Campbell, K.S.and Karasuyama, H.: "The Igalpha/Igbeta heterodimer on mu-negative proB cells is component for transducing signals to induce early B cell differentiation." Immunity. 7. 559-570 (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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