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Published on: January 20, 2019
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LTβR overexpression promotes plasma cell accumulation.
Jessica A Kotov1, Ying Xu1, Nicholas D Carey2
1Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, CA, United States of America.
Plos One
|August 4, 2022
Summary
Lymphotoxin beta receptor (LTBR) overexpression enhances plasma cell formation and survival, suggesting a role in multiple myeloma development. Amplification of the LTBR locus may drive this cancer by increasing NF-kB activity.
Area of Science:
- Immunology
- Molecular Biology
- Cancer Biology
Background:
- Multiple myeloma (MM) is a plasma cell malignancy with varied genetic causes.
- Lymphotoxin beta receptor (LTBR) is crucial for lymphoid tissue but its role in plasma cells is unclear.
Purpose of the Study:
- To investigate the function of LTBR in plasma cells (PCs).
- To determine if LTBR amplification contributes to multiple myeloma pathogenesis.
Main Methods:
- Compared Ltbr mRNA levels in mouse PCs and follicular B cells.
- Assessed PC responses in Ltbr-deficient mice.
- Examined the effects of LTBR overexpression (OE) on PC formation in vitro and in vivo.
- Analyzed gene expression changes (Nfkb2, Bcl2, Mcl1) in LTBR OE PCs.
Main Results:
- Ltbr mRNA was upregulated in mouse PCs.
- LTBR deficiency did not impair PC responses to immunogens.
- LTBR OE enhanced PC formation in vitro and increased antigen-specific PC responses in vivo.
- LTBR OE PCs showed increased Nfkb2, Bcl2, and Mcl1 expression.
Conclusions:
- LTBR is functional in plasma cells and promotes their formation and survival.
- LTBR overexpression enhances PC responses, potentially through Nfkb2 and NF-kB pathway activation.
- Ltbr gene amplification may contribute to multiple myeloma by increasing NF-kB activity and promoting PC survival.
