CD137L and CD4 T cells limit BCL6-expressing pre-germinal center B cell expansion and BCL6-driven B cell malignancy

Zhoujie Ding, Isaak Quast, Feng Yan, Yang Liao, Catherine Pitt, Kristy O'Donnell, Marcus J. Robinson, Wei Shi, Axel Kallies, Dimitra Zotos, David M. Tarlinton

Research output: Contribution to journalArticleResearchpeer-review


Aberrant expression of the proto-oncogene BCL6 is a driver of tumorigenesis in diffuse large B cell lymphoma (DLBCL). Mice overexpressing BCL6 from the B cell-specific immunoglobulin heavy chain μ intron promoter (Iμ-Bcl6Tg/+) develop B cell lymphomas with features typical of human DLBCL. While the development of B cell lymphoma in these mice is tightly controlled by T cells, the mechanisms of this immune surveillance are poorly understood. Here we show that CD4 T cells contribute to the control of lymphoproliferative disease in lymphoma-prone Iμ-Bcl6Tg/+ mice. We reveal that this CD4 T cell immuno-surveillance requires signaling by the co-stimulatory molecule CD137 ligand (CD137L; also known as 4-1BBL), which may promote the transition of pre-malignant B cells with an activated phenotype into the germinal center stage via reverse signaling, preventing their hazardous accumulation. Thus, CD137L-mediated CD4 T cell immuno-surveillance adds another layer of protection against B cell malignancy to that provided by CD8 T cell cytotoxicity.

Original languageEnglish
Pages (from-to)705-717
Number of pages13
JournalImmunology and Cell Biology
Issue number9
Publication statusPublished - Oct 2022


  • B cell malignancy
  • BCL6
  • CD137L
  • CD4 T cells
  • tumor immunity

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