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Blood. 2019 Jun 13;133(24):2597-2609. doi: 10.1182/blood.2018880138. Epub 2019 Apr 8.

Chronic CD30 signaling in B cells results in lymphomagenesis by driving the expansion of plasmablasts and B1 cells.

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Research Unit Gene Vectors, Helmholtz Center Munich, German Research Center for Environmental Health GmbH, Munich, Germany.
Department for Experimental and Laboratory Animal Pathology, Medical University Vienna, Vienna, Austria.
Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria.
Unit of Pathology of Laboratory Animals, University of Veterinary Medicine Vienna, Vienna, Austria.
CBMed Core Lab2, Medical University of Vienna, Vienna, Austria.
Research Unit Analytical Pathology, Helmholtz Center Munich, German Research Center for Environmental Health GmbH, Munich, Germany.
Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.
Experimental Hematology, TranslaTUM, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany; and.
German Cancer Research Center, German Cancer Consortium, Heidelberg, Germany.


CD30 is expressed on a variety of B-cell lymphomas, such as Hodgkin lymphoma, primary effusion lymphoma, and a diffuse large B-cell lymphoma subgroup. In normal tissues, CD30 is expressed on some activated B and T lymphocytes. However, the physiological function of CD30 signaling and its contribution to the generation of CD30+ lymphomas are still poorly understood. To gain a better understanding of CD30 signaling in B cells, we studied the expression of CD30 in different murine B-cell populations. We show that B1 cells expressed higher levels of CD30 than B2 cells and that CD30 was upregulated in IRF4+ plasmablasts (PBs). Furthermore, we generated and analyzed mice expressing a constitutively active CD30 receptor in B lymphocytes. These mice displayed an increase in B1 cells in the peritoneal cavity (PerC) and secondary lymphoid organs as well as increased numbers of plasma cells (PCs). TI-2 immunization resulted in a further expansion of B1 cells and PCs. We provide evidence that the expanded B1 population in the spleen included a fraction of PBs. CD30 signals seemed to enhance PC differentiation by increasing activation of NF-κB and promoting higher levels of phosphorylated STAT3 and STAT6 and nuclear IRF4. In addition, chronic CD30 signaling led to B-cell lymphomagenesis in aged mice. These lymphomas were localized in the spleen and PerC and had a B1-like/plasmablastic phenotype. We conclude that our mouse model mirrors chronic B-cell activation with increased numbers of CD30+ lymphocytes and provides experimental proof that chronic CD30 signaling increases the risk of B-cell lymphomagenesis.


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