Mitochondrial uncoupling protein 2 protects splenocytes from oxidative stress-induced apoptosis during pathogen activation

• The levels of IgG epitope genes are significantly less in UCP2-KO mice.
• UCP2-KO splenocytes are more susceptible to pathogen activation-induced apoptosis.
• ROS level in activated UCP2-KO splenocytes is significantly higher than that in WT.
• We demonstrate UCP2 protects splenocytes from oxidative stress-induced apoptosis.

Accumulating evidences suggested that mitochondrial uncoupling protein 2 (UCP2) is involved in host defense in parasite infection, inflammation, and autoimmune responses. However, it remains unknown whether UCP2 is participated in the modulation of humoral immune response. Here we used quantitative PCR, ELISA, TUNEL assay, flow cytometry, etc. to study the role of UCP2 in spleen B lymphocytes during pathogen activation and obtained following results. First, UCP2 is highly expressed in splenocytes and its expression level in splenocytes is rapidly increased when the cells are activated by lipopolysaccharide (LPS) in vivo or by LPS plus cytokines in vitro. Second, in contrast to the wild type (WT) littermates, the UCP2 knockout (UCP2-KO) mice show an impaired humoral immune response when they are challenged by pathogen. Although UCP2-KO mice produce a normal level of IgM, the levels of IgGs are significantly less than those of WT littermates. Third, splenocytes from UCP2-KO mice are more susceptible to pathogen activation-induced apoptosis, and the high level of reactive oxygen species (ROS) in UCP2-KO mice may be the cause for the apoptosis. In conclusion, our study demonstrates that mitochondrial UCP2 plays a critical role in protecting splenocytes from oxidative stress-induced apoptosis during pathogen activation.