Impaired receptor editing in the primary B cell repertoire of BASH-deficient mice

Katsuhiko Hayashi, Takuya Nojima, Ryo Goitsuka, Daisuke Kitamura

研究成果: ジャーナルへの寄稿記事

20 引用 (Scopus)

抄録

The editing of B cell Ag receptor (BCR) through successive rearrangements of Ig genes has been considered to be a major mechanism for the central B cell tolerance, which precludes appearance of self-reactive B cells, through studies using anti-self-Ig transgenic/knock-in mouse systems. However, contribution of the receptor editing in the development of the normal B cell repertoire remains unclear. In addition, the signaling pathway directing this event is unknown. In this study, we demonstrate that receptor editing in anti-DNA Ig knock-in mice is impaired in the absence of an adaptor protein BASH (BLNK/SLP-65) that is involved in BCR signaling. Remarkably, the supposed hallmarks of receptor editing such as Igλ chain expression, recombination sequence rearrangements at Igκ loci, and presence of in-frame VκJκ joins in the Igκ loci inactivated by the recombination sequence rearrangements, were all diminished in BASH-deficient mice with unmanipulated Ig loci. BCR ligation-induced Igλ gene recombination in vitro was also impaired in BASH-deficient B cells. Furthermore, the BASH-deficient mice showed an excessive Ab response to a DNA carrier immunization, suggesting the presence of unedited DNA-reactive B cells in the periphery. These results not only define a signaling pathway required for receptor editing but indicate that the BCR-signaled receptor editing indeed operates in the development of normal B cell repertoire and contributes to establishing the B cell tolerance.

元の言語英語
ページ(範囲)5980-5988
ページ数9
ジャーナルJournal of Immunology
173
発行部数10
DOI
出版物ステータス出版済み - 11 15 2004
外部発表Yes

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B-Lymphocytes
Genetic Recombination
Immunoglobulin Genes
DNA
Ligation
Immunization

All Science Journal Classification (ASJC) codes

  • Immunology

これを引用

Impaired receptor editing in the primary B cell repertoire of BASH-deficient mice. / Hayashi, Katsuhiko; Nojima, Takuya; Goitsuka, Ryo; Kitamura, Daisuke.

:: Journal of Immunology, 巻 173, 番号 10, 15.11.2004, p. 5980-5988.

研究成果: ジャーナルへの寄稿記事

Hayashi, Katsuhiko ; Nojima, Takuya ; Goitsuka, Ryo ; Kitamura, Daisuke. / Impaired receptor editing in the primary B cell repertoire of BASH-deficient mice. :: Journal of Immunology. 2004 ; 巻 173, 番号 10. pp. 5980-5988.
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