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

ABSTRACT: 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.

SUBMITTER: Kuhn LB

PROVIDER: S-EPMC9468873 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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

Kuhn Laura B LB Valentin Stefanie S Stojanovic Kristina K Strobl Daniel C DC Babushku Tea T Wang Yan Y Rambold Ursula U Scheffler Laura L Grath Sonja S John-Robbert Dorothy D Blum Helmut H Feuchtinger Annette A Blutke Andreas A Weih Falk F Kitamura Daisuke D Rad Roland R Strobl Lothar J LJ Zimber-Strobl Ursula U

Frontiers in immunology 20220830

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 ...[more]

PMID: 36110848

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Dataset Information

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

Publications

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

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