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Kuhn, L. ; Valentin, S. ; Stojanovic, K. ; Strobl, D.C. ; Babushku, T. ; Wang, Y. ; Rambold, U. ; Scheffler, L. ; Grath, S.* ; John-Robbert, D.* ; Blum, H.* ; Feuchtinger, A. ; Blutke, A. ; Weih, F.* ; Kitamura, D.* ; Rad, R.* ; Strobl, L.J. ; Zimber-Strobl, U.

RelB contributes to the survival, migration and lymphomagenesis of B cells with constitutively active CD40 signaling.

Front. Immunol. 13:913275 (2022)
Verlagsversion Forschungsdaten DOI
Open Access Gold
Creative Commons Lizenzvertrag
Activation of CD40-signaling contributes to the initiation, progression and drug resistance of B cell lymphomas. We contributed to this knowledge by showing that constitutive CD40-signaling in B cells induces B cell hyperplasia and finally B cell lymphoma development in transgenic mice. CD40 activates, among others, the non-canonical NF-ĸB signaling, which is constitutively activated in several human B cell lymphomas and is therefore presumed to contribute to lymphopathogenesis. This prompted us to study the regulatory role of the non-canonical NF-ĸB transcription factor RelB in lymphomagenesis. To this end, we crossed mice expressing a constitutively active CD40 receptor in B cells with conditional RelB-KO mice. Ablation of RelB attenuated pre-malignant B cell expansion, and resulted in an impaired survival and activation of long-term CD40-stimulated B cells. Furthermore, we found that hyperactivation of non-canonical NF-кB signaling enhances the retention of B cells in the follicles of secondary lymphoid organs. RNA-Seq-analysis revealed that several genes involved in B-cell migration, survival, proliferation and cytokine signaling govern the transcriptional differences modulated by the ablation of RelB in long-term CD40-stimulated B cells. Inactivation of RelB did not abrogate lymphoma development. However, lymphomas occurred with a lower incidence and had a longer latency period. In summary, our data suggest that RelB, although it is not strictly required for malignant transformation, accelerates the lymphomagenesis of long-term CD40-stimulated B cells by regulating genes involved in migration, survival and cytokine signaling.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cd40 ; Non-canonical Nf-kappa B-signaling ; Relb ; Il9r ; Transgenic Mice ; B Cell Lymphoma ; Migration ; Lilrb4
ISSN (print) / ISBN 1664-3224
e-ISSN 1664-3224
Quellenangaben Band: 13, Heft: , Seiten: , Artikelnummer: 913275 Supplement: ,
Verlag Frontiers
Begutachtungsstatus Peer reviewed
Förderungen Deutsche Forschungsgemeinschaft
Deutsche Krebshilfe