Differences in the quality of BCR signaling control key steps of B cell maturation and differentiation. Endogenously produced H2O2 is thought to fine tune the level of BCR signaling by reversibly inhibiting phosphatases. However, relatively little is known about how B cells at different stages sense and respond to such redox cues. In this study, we used phospho-specific flow cytometry and high-dimensional mass cytometry (CyTOF) to compare BCR signaling responses in mature human tonsillar B cells undergoing germinal center (GC) reactions. GC B cells, in contrast to mature naive B cells, memory B cells, and plasmablasts, were hypersensitive to a range of H2O2 concentrations and responded by phosphorylating SYK and other membrane-proximal BCR effectors in the absence of BCR engagement. These findings reveal that stage-specific redox responses distinguish human GC B cells.
This work was supported by National Institutes of Health/National Cancer Institute Grants R00CA143231, R25CA13644, and P30CA068485 and by the Norwegian Cancer Society.
The online version of this article contains supplemental material.
- Received April 28, 2015.
- Accepted June 11, 2015.
- Copyright © 2015 by The American Association of Immunologists, Inc.