Essential requirement for nicastrin in marginal zone and B-1 B cell development
Abstract
Follicular B cells generally require T cell help to contribute to adaptive immunity, producing several isotypes of immunoglobulins that carry out distinct effector functions. Two specialized B cell subsets, marginal zone (MZ) and B-1 B cells, arise from different developmental steps and have different functions. They become activated to produce antibodies without T cell help and are the major sources of plasma IgM. We identified a viable missense allele of Ncstn in a forward genetic screen. We discovered that the development of MZ and B-1 B cells, TI antibody response, fur pigmentation, and intestinal homeostasis critically depend on the glycosylation status of NCSTN and the catalytic activity of γ-secretase toward its substrate Notch, a critical receptor in numerous developmental decisions.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- March 2020
- DOI:
- 10.1073/pnas.1916645117
- Bibcode:
- 2020PNAS..117.4894C