The LRF transcription factor regulates mature B cell development and the germinal center response in mice

Nagisa Sakurai, Manami Maeda, Sung Uk Lee, Yuichi Ishikawa, Min Li, John C. Williams, Lisheng Wang, Leila Su, Mai Suzuki, Toshiki I. Saito, Shigeru Chiba, Stefano Casola, Hideo Yagita, Julie Teruya-Feldstein, Shinobu Tsuzuki, Ravi Bhatia, Takahiro Maeda

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

B cells play a central role in immune system function. Deregulation of normal B cell maturation can lead to the development of autoimmune syndromes as well as B cell malignancies. Elucidation of the molecular features of normal B cell development is important for the development of new target therapies for autoimmune diseases and B cell malignancies. Employing B cell-specific conditional knockout mice, we have demonstrated here that the transcription factor leukemia/lymphoma-related factor (LRF) forms an obligate dimer in B cells and regulates mature B cell lineage fate and humoral immune responses via distinctive mechanisms. Moreover, LRF inactivation in transformed B cells attenuated their growth rate. These studies identify what we believe to be a new key factor for mature B cell development and provide a rationale for targeting LRF dimers for the treatment of autoimmune diseases and B cell malignancies.

Original languageEnglish
Pages (from-to)2583-2598
Number of pages16
JournalJournal of Clinical Investigation
Volume121
Issue number7
DOIs
Publication statusPublished - Jul 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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