TY - JOUR
T1 - Notch signaling induces a transcriptionally permissive state at the Complement C3d Receptor 2 (CR2) promoter in a pre-B cell model
AU - Ng, Han Leng
AU - Taylor, Rhonda L.
AU - Cheng, Jessica
AU - Abraham, Lawrence J.
AU - Quail, Elizabeth
AU - Cruickshank, Mark N.
AU - Ulgiati, Daniela
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
KW - B cells
KW - Complement
KW - Gene regulation
KW - Human
KW - Molecular biology
KW - Transcription factors
UR - http://www.scopus.com/inward/record.url?scp=85097967752&partnerID=8YFLogxK
U2 - 10.1016/j.molimm.2020.10.001
DO - 10.1016/j.molimm.2020.10.001
M3 - Article
C2 - 33129017
AN - SCOPUS:85097967752
VL - 128
SP - 150
EP - 164
JO - Molecular Immunology
JF - Molecular Immunology
SN - 0161-5890
ER -