Journal article
Mitochondrial function provides instructive signals for activation-induced B-cell fates
KJ Jang, H Mano, K Aoki, T Hayashi, A Muto, Y Nambu, K Takahashi, K Itoh, S Taketani, SL Nutt, K Igarashi, A Shimizu, M Sugai
Nature Communications | Published : 2015
DOI: 10.1038/ncomms7750
Open access
Abstract
During immune reactions, functionally distinct B-cell subsets are generated by stochastic processes, including class-switch recombination (CSR) and plasma cell differentiation (PCD). In this study, we show a strong association between individual B-cell fates and mitochondrial functions. CSR occurs specifically in activated B cells with increased mitochondrial mass and membrane potential, which augment mitochondrial reactive oxygen species (mROS), whereas PCD occurs in cells with decreased mitochondrial mass and potential. These events are consequences of initial slight changes in mROS in mitochondriahigh B-cell populations. In CSR-committed cells, mROS attenuates haeme synthesis by inhibitin..
View full abstractGrants
Awarded by Australian Research Council
Funding Acknowledgements
We thank Drs F. Alt (Harvard University), U. Basu (Harvard University) and J. Chaudhuri (Memorial Sloan-Kettering Cancer Center) for providing AID antibody; Drs K. Iwai (Kyoto University), Y. Sasaki (Kyoto University), H. Arakawa (National Cancer Center) and Y. Yokota (Fukui University) for discussion of the findings; Drs K. Ochiai (Tohoku University) and Y. Yokota (Fukui University) for critical reading of the manuscript; Dr M. Minami (Kyoto University) for comments on mitochondrial assay; Ms K. Furuta and Mr H. Koda (Kyoto University) for technical assistance in electron microscopy; Drs Okuno (Kyoto University) and Fukuura (PRIMETECH Corp) for the XF96 assay; Dr Takatani (Kyoto University) for comments on this study; and Mr K. Yoshida (Kyoto University) for supporting experiments. We thank Enago (www.enago.jp) for English language review. This work was supported in part by grants-in-aid for Science Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan. S.L.N. was supported by an Australian Research Council Future Fellowship and Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIIS.