Mitochondrial reactive oxygen species suppress humoral immune response through reduction of CD19 expression in B cells in mice

作者：Ogura Masato; Inoue Takeshi; Yamaki Junko; Homma Miwako K; Kurosaki Tomohiro; Homma Yoshimi

来源：European Journal of Immunology, 2017, 47(2): 406-418.

DOI：10.1002/eji.201646342

• B cells
• Gender difference
• Immune responses
• Mitochondria
• ROS

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 (bSDHA(Y215F)). 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, IgG(1), and IgG(3), and affinity maturation of IgG(1) 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 PLC gamma 2, 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.

• 出版日期2017-2
• 单位RIKEN