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Title: CD137L and CD4 T cells limit BCL6-expressing pre-germinal center B cell expansion and BCL6-driven B cell malignancy.
Austin Authors: Ding, Zhoujie;Quast, Isaak;Yan, Feng;Liao, Yang;Pitt, Catherine;O-Donnell, Kristy;Robinson, Marcus J;Shi, Wei;Kallies, Axel;Zotos, Dimitra;Tarlinton, David M
Affiliation: The Peter Doherty Institute, University of Melbourne, Melbourne, VIC, Australia..
Department of Immunology & Pathology, Alfred Medical Research and Education Precinct, Monash University, Melbourne, VIC, Australia..
Australian Centre for Blood Diseases, Central Clinical School, Monash University, Melbourne, VIC, Australia..
Olivia Newton-John Cancer Research Institute
Issue Date: 2-Aug-2022
Date: 2022
Publication information: Immunology and Cell Biology 2022-10; 100(9): 705-717
Abstract: 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 B cell lymphoma development 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 signalling, 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.
DOI: 10.1111/imcb.12578
ORCID: 0000-0001-6517-8537
Journal: Immunology and Cell Biology
PubMed URL: 35916066
PubMed URL:
Type: Journal Article
Subjects: B cell malignancy
CD4 T cells
tumour immunity
Appears in Collections:Journal articles

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