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A Distinct Subset of Fibroblastic Stromal Cells Constitutes the Cortex-Medulla Boundary Subcompartment of the Lymph Node.

Arata Takeuchi | Madoka Ozawa | Yasuhiro Kanda | Mina Kozai | Izumi Ohigashi | Yoichi Kurosawa | Md Azizur Rahman | Toshihiko Kawamura | Yuto Shichida | Eiji Umemoto | Masayuki Miyasaka | Burkhard Ludewig | Yousuke Takahama | Takashi Nagasawa | Tomoya Katakai
Frontiers in immunology | 2018

The spatiotemporal regulation of immune responses in the lymph node (LN) depends on its sophisticated tissue architecture, consisting of several subcompartments supported by distinct fibroblastic stromal cells (FSCs). However, the intricate details of stromal structures and associated FSC subsets are not fully understood. Using several gene reporter mice, we sought to discover unrecognized stromal structures and FSCs in the LN. The four previously identified FSC subsets in the cortex are clearly distinguished by the expression pattern of reporters including PDGFRβ, CCL21-ser, and CXCL12. Herein, we identified a unique FSC subset expressing both CCL21-ser and CXCL12 in the deep cortex periphery (DCP) that is characterized by preferential B cell localization. This subset was clearly different from CXCL12highLepRhigh FSCs in the medullary cord, which harbors plasma cells. B cell localization in the DCP was controlled chiefly by CCL21-ser and, to a lesser extent, CXCL12. Moreover, the optimal development of the DCP as well as medulla requires B cells. Together, our findings suggest the presence of a unique microenvironment in the cortex-medulla boundary and offer an advanced view of the multi-layered stromal framework constructed by distinct FSC subsets in the LN.

Pubmed ID: 30333825

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GraphPad Prism (tool)

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Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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Imaris (tool)

RRID:SCR_007370

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RRID:SCR_008520

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Miltenyi Biotec (tool)

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laboratory mouse with name C57BL/6JJcl from MGI.

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