B-cell-activating factor inhibits CD20-mediated and B-cell receptor-mediated apoptosis in human B cells

Yohei Saito, Yoshitaka Miyagawa, Keiko Onda, Hideki Nakajima, Ban Sato, Yasuomi Horiuchi, Hajime Okita, Yohko U. Katagiri, Masahiro Saito, Toshiaki Shimizu, Junichiro Fujimoto, Nobutaka Kiyokawa

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18 Citations (Scopus)

Abstract

B-cell-activating factor (BAFF) is a survival and maturation factor for B cells belonging to the tumour necrosis factor superfamily. Among three identified functional receptors, the BAFF receptor (BAFF-R) is thought to be responsible for the effect of BAFF on B cells though details of how remain unclear. We determined that a hairy-cell leukaemia line, MLMA, expressed a relatively high level of BAFF-R and was susceptible to apoptosis mediated by either CD20 or B-cell antigen receptor (BCR). Using MLMA cells as an in vitro model of mature B cells, we found that treatment with BAFF could inhibit apoptosis mediated by both CD20 and BCR. We also observed, using immunoblot analysis and microarray analysis, that BAFF treatment induced activation of nuclear factor-κB2 following elevation of the expression level of Bcl-2, which may be involved in the molecular mechanism of BAFF-mediated inhibition of apoptosis. Interestingly, BAFF treatment was also found to induce the expression of a series of genes, such as that for CD40, related to cell survival, suggesting the involvement of a multiple mechanism in the BAFF-mediated anti-apoptotic effect. MLMA cells should provide a model for investigating the molecular basis of the effect of BAFF on B cells in vitro and will help to elucidate how B cells survive in the immune system in which BAFF-mediated signalling is involved.

Original languageEnglish
Pages (from-to)570-590
Number of pages21
JournalImmunology
Volume125
Issue number4
DOIs
Publication statusPublished - 2008 Dec

Keywords

  • Apoptosis
  • B-cell receptor
  • B-cell-activating factor
  • Bcl-2
  • CD20

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Saito, Y., Miyagawa, Y., Onda, K., Nakajima, H., Sato, B., Horiuchi, Y., Okita, H., Katagiri, Y. U., Saito, M., Shimizu, T., Fujimoto, J., & Kiyokawa, N. (2008). B-cell-activating factor inhibits CD20-mediated and B-cell receptor-mediated apoptosis in human B cells. Immunology, 125(4), 570-590. https://doi.org/10.1111/j.1365-2567.2008.02872.x