| First Author | Ogura M | Year | 2017 |
| Journal | Eur J Immunol | Volume | 47 |
| Issue | 2 | Pages | 406-418 |
| PubMed ID | 27883180 | Mgi Jnum | J:246252 |
| Mgi Id | MGI:5922162 | Doi | 10.1002/eji.201646342 |
| Citation | Ogura M, et al. (2017) Mitochondrial reactive oxygen species suppress humoral immune response through reduction of CD19 expression in B cells in mice. Eur J Immunol 47(2):406-418 |
| abstractText | Reactive oxygen species (ROS) are implicated in the modulation of diverse processes including immune responses. To evaluate the effects of metabolic ROS produced by mitochondria on B-cell function and development, we created transgenic (Tg) mice expressing a phosphorylation-defective mutant of succinate dehydrogenase A in B cells (bSDHAY215F ). Splenic B cells in male, but not female, bSDHAY215F mice produced three times more ROS than those in the control mice, and had decreased production of IgM, IgG1 , and IgG3 , and affinity maturation of IgG1 against T-cell-dependent antigens. Following immunization, the male bSDHAY215F mice further displayed suppressed germinal center (GC) formation, and proliferation of GC B cells. Signaling analysis revealed defects in the intrinsic BCR responses, such as activation of Lyn, Btk, and PLCgamma2, thus resulting in reduced intracellular Ca2+ mobilization. Notably, the expression levels of B-cell co-receptor CD19 and its interaction with Lyn after BCR ligation were significantly reduced in B cells from male bSDHAY215F mice. These results suggest that mitochondrial ROS suppress humoral immune responses through reduction of CD19 expression and resultant BCR signaling in B cells. Therefore, B-cell immunity may be more labile to oxidative stress in male mice than in female mice. |
