Myeloid cells are central players in innate immunity and inflammation. Their function is regulated by the adaptor protein TRAF3. We previously reported that aging myeloid cell-specific TRAF3-deficient (M-Traf3-/-) mice spontaneously develop chronic inflammation and B-cell lymphoma. Here we aimed to identify the internal trigger of this disease phenotype in these mice. We first detected gut microbiota dysbiosis and transmigration of commensal bacteria to the liver in aging M-Traf3-/- mice. Interestingly, depletion of commensal bacteria using antibiotics effectively prevented B-cell lymphoma development in these mice. Systemic IgG responses against commensal bacteria were induced and the IgH CDR3 sequences of malignant B-cell clones of M-Traf3-/- mice showed high homology to prevalent bacteria-reactive Ig clonotypes. Furthermore, M-Traf3-/- mice with B-cell lymphomas exhibited high serum titers of antibodies against commensal bacteria. Together, our findings offer insights into the mechanisms underlying increased risks of B-cell lymphomagenesis observed in patients with compromised innate immunity
Biography:
Dr. Ping Xie is an Associate Professor in the Department of Cell Biology and Neuroscience at Rutgers University. Dr. Xie received the PhD from the Hong Kong University of Science & Technology, followed by postdoctoral work at the University of Illinois at Chicago and the University of Iowa. She joined the faculty of Department of Cell Biology and Neuroscience at Rutgers University in 2008. She was a Special Fellow of the Leukemia & Lymphoma Society. Her laboratory’s research has been supported by the USA NIH, DoD, New Jersey Commission on Cancer Research, and the Cancer Institute of New Jersey.
