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

Item Type:	Article
Title:	Chronic CD30-signaling in B cells results in lymphomagenesis by driving the expansion of plasmablasts and B1 cells
Creators Name:	Sperling, S.A. and Fiedler, P. and Lechner, M. and Pollithy, A. and Ehrenberg, S. and Schiefer, A.I. and Kenner, L. and Feuchtinger, A. and Kühn, R. and Swinerd, G. and Schmidt-Supprian, M. and Strobl, L.J. and Zimber-Strobl, U.
Abstract:	CD30 is expressed on a variety of B-cell lymphomas such as Hodgkin's lymphoma, primary effusion lymphoma, and a subgroup of diffuse large B-cell lymphoma. 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-positive 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 express higher levels of CD30 than B2 cells and that CD30 is upregulated in IRF4(+) plasmablasts (PB). Furthermore, we generated and analyzed mice expressing a constitutively active CD30-receptor in B lymphocytes. These mice displayed an increase of B1 cells in the peritoneal cavity (PerC) and in secondary lymphoid organs as well as increased numbers of plasma cells (PC). TI-2-immunization resulted in a further expansion of B1 cells and PC. We provide evidence that the expanded B1 population in the spleen includes a fraction of PB. CD30 signals appeared to enhance PC-differentiation by increasing activation of NF-κB, higher levels of phosphorylated STAT3 and STAT6 and of 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.
Keywords:	B-Cell Lymphoma, B-Lymphocytes, B-Lymphoid Precursor Cells, Ki-1 Antigen, Neoplastic Cell Transformation, Plasma Cells, Signal Transduction, Transgenic Mice, Animals, Mice
Source:	Blood
ISSN:	0006-4971
Publisher:	American Society of Hematology
Volume:	133
Number:	24
Page Range:	2597-2609
Date:	13 June 2019
Official Publication:	https://doi.org/10.1182/blood.2018880138
PubMed:	View item in PubMed

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