T cell leukemia/lymphoma 1 and galectin-1 regulate survival/cell death pathways in human naive and IgM+ memory B cells through altering balances in Bcl-2 family proteins

Siamak Jabbarzadeh Tabrizi, Hiroaki Niiro, Mariko Masui, Goichi Yoshimoto, Tadafumi Iino, Yoshikane Kikushige, Takahiro Wakasaki, Eishi Baba, Shinji Shimoda, Toshihiro Miyamoto, Toshiro Hara, Koichi Akashi

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

BCR signaling plays a critical role in purging the self-reactive repertoire, or in rendering it anergic to establish self-tolerance in the periphery. Differences in self-reactivity between human naive and IgM + memory B cells may reflect distinct mechanisms by which BCR signaling dictates their survival and death. Here we demonstrate that BCR stimulation protected naive B cells from apoptosis with induction of prosurvival Bcl-2 family proteins, Bcl-xL and Mcl-1, whereas it rather accelerated apoptosis of IgM+ memory B cells by inducing proapoptotic BH3-only protein Bim. We found that BCR-mediated PI3K activation induced the expression of Mcl-1, whereas it inhibited Bim expression in B cells. Phosphorylation of Akt, a downstream molecule of PI3K, was more sustained in naive than IgM+ memory B cells. Abundant expression of T cell leukemia/lymphoma 1 (Tcl1), an Akt coactivator, was found in naive B cells, and enforced expression of Tcl1 induced a high level of Mcl-1 expression, resulting in prolonged B cell survival. In contrast, Galectin-1 (Gal-1) was abundantly expressed in IgM+ memory B cells, and inhibited Akt phosphorylation, leading to Bim up-regulation. Enforced expression of Gal-1 induced accelerated apoptosis in B cells. These results suggest that a unique set of molecules, Tcl1 and Gal-1, defines distinct BCR signaling cascades, dictating survival and death of human naive and IgM+ memory B cells.

Original languageEnglish
Pages (from-to)1490-1499
Number of pages10
JournalJournal of Immunology
Volume182
Issue number3
DOIs
Publication statusPublished - Feb 1 2009

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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