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

Katsuhiko Hayashi, Takuya Nojima, Ryo Goitsuka, Daisuke Kitamura

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)5980-5988
Number of pages9
JournalJournal of Immunology
Volume173
Issue number10
DOIs
Publication statusPublished - Nov 15 2004
Externally publishedYes

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B-Lymphocytes
Genetic Recombination
Immunoglobulin Genes
DNA
Ligation
Immunization

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

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

In: Journal of Immunology, Vol. 173, No. 10, 15.11.2004, p. 5980-5988.

Research output: Contribution to journalArticle

Hayashi, Katsuhiko ; Nojima, Takuya ; Goitsuka, Ryo ; Kitamura, Daisuke. / Impaired receptor editing in the primary B cell repertoire of BASH-deficient mice. In: Journal of Immunology. 2004 ; Vol. 173, No. 10. pp. 5980-5988.
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