Tumor necrosis factor receptor associated factor 3 (TRAF3) is an adaptor protein that plays an important role in B cell homeostasis. TRAF3 deletions or inactivating mutations are common in human B cell malignancies. TRAF3 negatively regulates several receptors in human B cells (including BAFFR, CD40, and IL-6). B cell specific TRAF3 knockout mice have enlarged spleens and lymph nodes and develop autoimmune manifestations as they age. B cells from B-cell specific TRAF3 deficient mice have markedly increased survival and autoantibody production. The B cell receptor (BCR) is crucial in B cells for proliferation and antibody production. Defects in BCR signaling can lead to autoimmunity and B cell malignancy.

The focus of my project is to investigate the role that TRAF3 plays in BCR signaling. Greater understanding of TRAF3 and BCR signaling may provide potential treatment targets or disease biomarkers for autoimmunity and B cell malignancies.

Whillock AL, Mambetsariev N, Lin WW, Stunz LL, Bishop GA. TRAF3 regulates the oncogenic proteins Pim2 and c-Myc to restrain survival in normal and malignant B cells. Sci Rep. 2019 Sep 9;9(1):12884. doi: 10.1038/s41598-019-49390-9. Erratum in: Sci Rep. 2019 Nov 20;9(1):17502. PubMed PMID: 31501481; PubMed Central PMCID: PMC6733949.

Bangalore-Prakash P, Stunz LL, Mambetsariev N, Whillock AL, Hostager BS, Bishop GA. The oncogenic membrane protein LMP1 sequesters TRAF3 in B-cell lymphoma cells to produce functional TRAF3 deficiency. Blood Adv. 2017 Dec 18;1(27):2712-2723. doi:10.1182/bloodadvances.2017009670. eCollection 2017 Dec 26. PubMed PMID: 29296923; PubMed Central PMCID: PMC5745131.