What is it about?

TRAF3 is a protein that plays an important role in preventing abnormal survival or activation of immune cells called B lymphocytes, which are our antibody-producing cells. Humans with one normal but one mutant TRAF3 gene have autoimmune disease, immunodeficiencies, and increased risk of B cell cancers. This study investigated impacts of decreased levels of B cell TRAF3, compared to complete loss or normal levels, upon B cell functions. Reduced TRAF3 protein in B cells had dose-dependent and important effects on B cells, highlighting the importance of TRAF3 in proper regulation of B cells. We also found that normal aging is associated with reduced TRAF3, possibly due to degradation of the TRAF3 protein induced by chronic inflammatory signals.

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Why is it important?

The results reveal the potential impact of age-related decline in TRAF3 on the increased frequency of disorders of B lymphocytes in older adults, and show that even a relative decrease in B cell TRAF3 is associated with abnormalities in B cell function. Treatment in a mouse model with a drug that inhibits TRAF3 protein degradation restored its normal levels, showing the importance of this mechanism in reduced TRAF3 levels in aging. This is consistent with the increased frequency of B cell-mediated autoimmunity and B cell cancers as we age.

Perspectives

These findings implicate levels of B cell TRAF3 as key to maintaining normal control of B cell functions and mitigating against contributions of B cells to pathologic conditions such as autoimmunity and malignancy, for which aging humans are at increased risk.

Gail Bishop
The University of Iowa

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This page is a summary of: Reduction of TRAF3 by heterozygosity or aging impacts B cell function, Proceedings of the National Academy of Sciences, August 2025, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2507217122.
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