التفاصيل البيبلوغرافية
العنوان: |
The Tetraspanin CD53 Regulates Early B Cell Development by Promoting IL-7R Signaling. |
المؤلفون: |
Greenberg, Zev J.1, Monlish, Darlene A.1, Bartnett, Rachel L.1, Yihu Yang2, Guomin Shen3, Weikai Li2, Bednarski, Jeffrey J.1, Schuettpelz, Laura G.1 Schuettpelz_l@wustl.edu |
المصدر: |
Journal of Immunology. Jan2020, Vol. 204 Issue 1, p58-67. 10p. |
مصطلحات موضوعية: |
*B cells, *B cell differentiation, *BONE marrow cells, *TETRASPANIN, *HEMATOPOIETIC stem cells, *TALL-1 (Protein) |
مستخلص: |
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. Cd53-/- mice have reduced surface expression of IL-7Rα 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. [ABSTRACT FROM AUTHOR] |
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