TY - JOUR
T1 - The tetraspanin CD53 regulates early B cell development by promoting IL-7R signaling
AU - Greenberg, Zev J.
AU - Monlish, Darlene A.
AU - Bartnett, Rachel L.
AU - Yang, Yihu
AU - Shen, Guomin
AU - Li, Weikai
AU - Bednarski, Jeffrey J.
AU - Schuettpelz, Laura G.
N1 - Funding Information:
This work was supported by funding from the Children’s Discovery Institute of Washington University and St. Louis Children’s Hospital (to L.G.S.), and the Training Program in Cellular and Molecular Biology (T32 GM007067-44) (to Z.J.G.).
Funding Information:
This work was supported by funding from the Children’s Discovery Institute of Washington University and St. Louis Children’s Hospital (to L.G.S.), and the Training Program in Cellular and Molecular Biology (T32 GM007067-44) (to Z.J.G.). We thank the Alvin J. Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital for the use of the Siteman Flow Cytometry Core and Immunomonitoring Laboratory, which provided assistance with CyTOF experiments. We thank Jillian Dunbar for graphical design assistance, Jackie Tucker-Davis and Al Sorensen for animal care, Kathryn Leonard for technical assistance, and Dr. S. Celeste Morley (Washington University) for valuable discussions. We thank the Genome Engineering and iPSC Center at Washington University for generation of the Cd53-/- mouse.
Publisher Copyright:
Copyright © 2019 by The American Association of Immunologists, Inc. All rights reserved.
PY - 2020
Y1 - 2020
N2 - The tetraspanin CD53 has been implicated in B cell development and function. CD53 is a transcriptional target of EBF1, a critical transcription factor for early B cell development. Further, human deficiency of CD53 results in recurrent infections and reduced serum Igs. Although prior studies have indicated a role for CD53 in regulating mature B cells, its role in early B cell development is not well understood. In this study, we show that CD53 expression, which is minimal on hematopoietic stem and progenitor cells, increases throughout bone marrow B cell maturation, and mice lacking CD53 have significantly decreased bone marrow, splenic, lymphatic, and peripheral B cells. Mixed bone marrow chimeras show that CD53 functions cell autonomously to promote B lymphopoiesis. Cd532/2 mice have reduced surface expression of IL-7Ra and diminished phosphatidylinositol 3 kinase and JAK/STAT signaling in prepro- and pro-B cells. Signaling through these pathways via IL-7R is essential for early B cell survival and transition from the pro-B to pre-B cell developmental stage. Indeed, we find increased apoptosis in developing B cells and an associated reduction in pre-B and immature B cell populations in the absence of CD53. Coimmunoprecipitation and proximity ligation studies demonstrate physical interaction between CD53 and IL-7R. Together, these data, to our knowledge, suggest a novel role for CD53 during IL-7 signaling to promote early B cell differentiation. The Journal of Immunology, 2020, 204: 58–67.
AB - The tetraspanin CD53 has been implicated in B cell development and function. CD53 is a transcriptional target of EBF1, a critical transcription factor for early B cell development. Further, human deficiency of CD53 results in recurrent infections and reduced serum Igs. Although prior studies have indicated a role for CD53 in regulating mature B cells, its role in early B cell development is not well understood. In this study, we show that CD53 expression, which is minimal on hematopoietic stem and progenitor cells, increases throughout bone marrow B cell maturation, and mice lacking CD53 have significantly decreased bone marrow, splenic, lymphatic, and peripheral B cells. Mixed bone marrow chimeras show that CD53 functions cell autonomously to promote B lymphopoiesis. Cd532/2 mice have reduced surface expression of IL-7Ra and diminished phosphatidylinositol 3 kinase and JAK/STAT signaling in prepro- and pro-B cells. Signaling through these pathways via IL-7R is essential for early B cell survival and transition from the pro-B to pre-B cell developmental stage. Indeed, we find increased apoptosis in developing B cells and an associated reduction in pre-B and immature B cell populations in the absence of CD53. Coimmunoprecipitation and proximity ligation studies demonstrate physical interaction between CD53 and IL-7R. Together, these data, to our knowledge, suggest a novel role for CD53 during IL-7 signaling to promote early B cell differentiation. The Journal of Immunology, 2020, 204: 58–67.
UR - http://www.scopus.com/inward/record.url?scp=85076876826&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1900539
DO - 10.4049/jimmunol.1900539
M3 - Article
C2 - 31748347
AN - SCOPUS:85076876826
VL - 204
SP - 58
EP - 67
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 1
ER -