Notch signaling induces a transcriptionally permissive state at the Complement C3d Receptor 2 (CR2) promoter in a pre-B cell model.

Han Leng Ng, Rhonda L Taylor, Jessica Cheng, Lawrence J Abraham, Elizabeth Quail, Mark N Cruickshank, Daniela Ulgiati

Molecular immunology 2020 Dec

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During mammalian lymphoid development, Notch signaling is necessary at multiple stages of T lymphopoiesis, including lineage commitment, and later stages of T cell effector differentiation. In contrast, outside of a defined role in the development of splenic marginal zone B cells, there is conflicting evidence regarding whether Notch signaling plays functional roles in other B cell sub-populations. Complement receptor 2 (CR2) modulates BCR-signaling and is tightly regulated throughout differentiation. During B lymphopoiesis, CR2 is detected on immature and mature B cells with high surface expression on marginal zone B cells. Here, we have explored the possibility that Notch regulates human CR2 transcriptional activity using in vitro models including a co-culture system, co-transfection gene reporters and chromatin accessibility assays. We provide evidence that Notch signaling regulates CR2 promoter activity in a mature B cell line, as well as the induction of endogenous CR2 mRNA in a non-expressing pre-B cell line. The dynamics of endogenous gene activation suggests additional unidentified factors are required to mediate surface CR2 expression on immature and mature B lineage cells. Copyright © 2020 Elsevier Ltd. All rights reserved.

Citation

Han Leng Ng, Rhonda L Taylor, Jessica Cheng, Lawrence J Abraham, Elizabeth Quail, Mark N Cruickshank, Daniela Ulgiati. Notch signaling induces a transcriptionally permissive state at the Complement C3d Receptor 2 (CR2) promoter in a pre-B cell model. Molecular immunology. 2020 Dec;128:150-164