骨髄内の免疫の未知の世界を可視化(A Window into the Hidden World of Immunity Inside Human Bone Marrow)

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2026-09-11 ジョージア工科大学

ジョージア工科大学とヴァンダービルト大学の研究チームは、ヒトの骨髄内で長期的な抗体産生を担う形質細胞(plasma cell)が、周囲の微小環境を探索し、生存に適した場所へ移動・定着する過程をリアルタイムで観察できる「骨髄オンチップ」を開発した。毛細血管ほどの微小流路を備えた3次元組織モデルに血管構造や骨髄特有の細胞環境を再現し、ヒト抗体産生細胞の動態を追跡した。その結果、細胞は血管周囲の「ニッチ」に集まり、停止と移動を繰り返しながら生存シグナルを探索することが判明した。また、血管周囲領域は細胞を誘引して生存を支え、骨表面に近い領域は移動・保持を調節するなど、異なる微小環境が協調して免疫記憶を形成することが示された。この技術は、ワクチンによる免疫の持続性、加齢による免疫低下、自己免疫疾患、慢性感染症、血液がんなどの研究に活用できる可能性がある。

A microscopic image shows lab grown bone marrow and blood vessels highlighted in gray and green weaving through a network of supportive cells and proteins highlighted in magenta.
Inside this lab-grown bone marrow, blood vessels (green and grey) thread through a network of supportive cells and proteins (magenta). Antibody-producing cells (blue) move through this landscape, finding the signals they need to survive and keep making antibodies.

<関連情報>

体外骨髄サブニッチはヒト抗体分泌細胞の運命に影響を与える Ex vivo bone marrow subniches influence the fate of human antibody-secreting cells

Liana Kramer, Zhonghao Dai, Jenna Corbin, Rachel Ringquist, […] , and Krishnendu Roy
Science Advances  Published:11 Sep 2026
DOI:https://doi.org/10.1126/sciadv.adz3976

Abstract

Long-term humoral immunity relies on long-lived plasma cells in the bone marrow (BM). However, the processes governing plasma cell transport, positioning, and longevity within the BM niche remain poorly understood, especially in humans. Most existing knowledge comes from mouse studies or limited human-based models, which makes translating findings to human biology challenging. Here, we introduce a physiologically relevant human bone marrow-on-a-chip (hBMOC) model to investigate the behavior and interactions of human immune organoid-derived antibody-secreting cells (ASCs) within the human BM microenvironment. The hBMOC model is microvascular and perfusable and incorporates both endosteal and perivascular niches. We demonstrate that human ASCs migrate through blood vessels, accumulating and clustering in perivascular areas where they are closely associated with critical survival factors. In addition, we found that the presence of the endosteal niche substantially affects human ASC survival, movement, and retention, underscoring the dynamic interactions among human BM subniches that regulate ASC activity. We observed that a subset of human ASCs exhibits a dynamic stop-and-go migration pattern partially regulated by CXCR4-CXCL12 signaling. These findings provide direct insight into human ASC biology that has remained poorly defined, including their niche-specific localization, survival, and migratory dynamics within a three-dimensional human bone marrow microenvironment. Our results emphasize the distinct and cooperative roles of perivascular and endosteal compartments in supporting human ASC fate, offering previously inaccessible mechanistic insights into how human BM niches regulate plasma cells. This work lays the groundwork for studying plasma cell aging, vaccine durability, and disease-related dysfunction in human ASC maintenance and persistence.

医療・健康
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