【博士論文】学術データベース

博士論文 / CXCL12-CXCR4 Axis Is Required for Contact-Mediated Human B Lymphoid and Plasmacytoid Dendritic Cell Differentiation but Not T Lymphoid Generation

著者

書誌事項

タイトル

CXCL12-CXCR4 Axis Is Required for Contact-Mediated Human B Lymphoid and Plasmacytoid Dendritic Cell Differentiation but Not T Lymphoid Generation

著者名

Minami Hirohito

学位授与大学

三重大学 (大学ID:0046) (CAT機関ID:KI000538)

取得学位

博士(医学)

学位授与番号

甲医学第1872号

学位授与年月日

2017-12-20

注記・抄録

We investigated the involvement of CXCL12-CXCR4 interactions in human lymphohematopoiesis by coculture with telomerized human stromal cells. XCR4 expression was low in CD34+CD38−CD45RA−CD10−CD7−CD19− immature hematopoietic stem/precursor cells (HSPCs) but higher in CD34+CD38−CD45RA CD10+CD7+/−CD19− early lymphoid precursors and even higher in CD34+CD38+CD45RA+CD10+CD7−CD19+ pro-B cells. Inhibition of the effect of stromal ell-produced CXCL12 by an anti-CXCR4-blocking Ab suppressed the generation of CD45RA+CD10−CD7+CD19− early T lymphoid precursors (ETPs) and D45RA+CD10+CD7−CD19+/− B lymphoid precursors on stromal cells, but it did not affect the generation of ETPs in conditioned medium of stromal cell cultures. Replating assays showed that contact with stromal cells was critical for HSPC-derived CD45RA+CD10+CD7−CD19− B lineage-biased precursors to differentiate into CD19+ pro-B cells, which was suppressed by the anti-CXCR4 Ab. Conversely, HSPC-derived ETPs possessed T and B lymphoid and onocytic differentiation potential; stromal cell contact was not required for their growth but rather promoted B lymphoid differentiation. The nti-CXCR4 Ab did not affect the growth of ETPs in conditioned medium, but it suppressed their B lymphoid differentiation on stromal cells. D14−CD11c−HLA-DR+CD123highCD303+ plasmacytoid dendritic cells developed from HSPCs and ETPs exclusively in contact with stromal cells, which was suppressed by the anti-CXCR4 Ab. These data indicate that CXCL12 plays an essential role in stromal cell contact-mediated B lymphoid and lasmacytoid dendritic cell differentiation from immature hematopoietic and early T lymphoid precursors with a multilineage ifferentiationpotential, but it does not participate in contact-independent generation of early T lymphoid precursors.

本文 / Department of Hematology and Oncology, Mie University Graduate School of Medicine

18p

内容の要旨・審査結果の要旨 / 三重大学大学院医学系研究科 生命医科学専攻 臨床医学系講座 血液・腫瘍内科学分野

各種コード

NII論文ID(NAID)

500001054935

NII著者ID(NRID)
  • 8000001172685
DOI (出版社)

10.4049/jimmunol.1700054

本文言語コード

eng

データ提供元

機関リポジトリ / NDLデジタルコレクション

博士論文 / 三重大学 / 医学

博士論文 / 三重大学

博士論文 / 医学

関連著者

博士論文 / 大学

博士論文 / 学位