Lyn signaling to upregulate GANP is critical for the survival of high-affinity B cells in germinal centers of lymphoid organs

Kazuhiko Kuwahara, Teruo Nakaya, Suchada Phimsen, Teppei Toda, Masahiro Kitabatake, Tomohiro Kaji, Toshitada Takemori, Takeshi Watanabe, Nobuo Sakaguchi

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5 Citations (Scopus)

Abstract

Signals through BCR and costimulatory molecules play essential roles in selecting high-affinity B cells with Ig V-region mutations in the germinal centers (GCs) of peripheral lymphoid organs. Lyn-deficient (lyn-/-) mice show impaired BCR signal triggering for cell proliferation and GC formation, causing hyper-IgM, and display autoimmunity after aging. In this study, we demonstrate that Lyn-mediated signaling to upregulate GANP is essential for the survival of mature GC-like (mGC) B cells with high-affinity type BCR mutations upon Ag immunization. Transgenic ganp expression into lyn-/- mice did not recover the Lyn-deficient phenotype with regard to B cell differentiation, serum Igs, and impaired GC formation in spleens after immunization with nitrophenyl-chicken γ-globulin, but it markedly rescued cell survival of mGC B cells by suppressing DNA damage, thereby increasing the frequency of the Trp33-to-Leu mutation in the IgVH-186.2 region and affinity maturation of nitrophenyl-binding B cells. GANP may play a critical role in Lyn-mediated signaling for the selection of high-affinity B cells in peripheral lymphoid organs.

Original languageEnglish
Pages (from-to)3472-3479
Number of pages8
JournalJournal of Immunology
Volume189
Issue number7
DOIs
Publication statusPublished - 01-10-2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Kuwahara, K., Nakaya, T., Phimsen, S., Toda, T., Kitabatake, M., Kaji, T., Takemori, T., Watanabe, T., & Sakaguchi, N. (2012). Lyn signaling to upregulate GANP is critical for the survival of high-affinity B cells in germinal centers of lymphoid organs. Journal of Immunology, 189(7), 3472-3479. https://doi.org/10.4049/jimmunol.1200649