ORIGINAL RESEARCH article
Front. Hematol.
Sec. Blood Cancer
Volume 4 - 2025 | doi: 10.3389/frhem.2025.1626886
Immune profile focusing on B-cell activating factor (BAFF) in B cell malignancies Authors
Provisionally accepted
- 1The University of Tokyo, Bunkyo, Japan
- 2Hokkaido University, Sapporo, Japan
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Background: B-cell activating factor (BAFF) is crucial for B cell survival, proliferation, and immunoglobulin secretion. However, its role in hematopoietic malignancies, particularly concerning B cell differentiation stages, remains unclear. This study explored the involvement of BAFF in B-cell malignancy progression and treatment response.Mouse malignant B-cell-linage cell lines A20 and MPC-11 OUAr cells were analyzed for responsiveness to BAFF both in vitro and in vivo. For an in vitro study, recombinant BAFF was examined for capacities rescuing those cells under drug-induced cytotoxicity. For an in vivo study, tumor progression induced by inoculation of the tumor cells was compared between wild-type and BAFF-knockout (BAFF-KO) mice. Transcriptomic analysis was conducted to assess immune responses and signaling pathways associated with BAFF-dependent tumor growth.Results: MPC 11 OUAr cells exhibited characteristics of more differentiated B cells, with a capacity of IgG secretion and elevated expression of B-cell maturation antigen (BCMA). In vitro, recombinant BAFF reduced drug-induced cytotoxicity on A20 cells but had no apparent effect on MPC 11 OUAr cells. In vivo, BAFF-KO mice exhibited better survival when administrated with MPC 11 OUAr cells that wild-type mice, whereas the opposite trend was observed when administrated with A20 cells. Transcriptomic analyses revealed that wild-type mice bearing MPC-11 OUAr tumors exhibited elevated expression of genes linked to angiogenesis and PI3K-Akt signaling pathway.Our findings suggest variable impacts of BAFF on B-cell-linage malignant cells depending on their cell types and highlight the complex role of BAFF in hematopoietic malignancies. Even when BAFF serves as a promoter of B-cell-linage tumor, its roles may not be restricted to direct effects to the malignant cells and may involve indirect effects to the other cells constituting the tumor microenvironment leading to the environment favorable to the malignant cells. The differential impact of BAFF on lymphoma subtypes underscores the need for targeted therapeutic strategies modulating BAFF signaling in B-cell malignancy.
Keywords: B cell, tumor, BAFF, mouse model, Knockout (KO) mice
Received: 12 May 2025; Accepted: 20 Aug 2025.
Copyright: © 2025 Tagami, Yamagishi, Fujii, Sanjoba and Goto. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yasuyuki Goto, The University of Tokyo, Bunkyo, Japan
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