Researchers have developed a bone marrow-on-a-chip platform coupled with a lymph node–mimicking organoid to study human plasma cell development, migration, and survival within bone marrow.

The model features a microfluidics-based vascularized bone marrow chip and a lymphoid organoid derived from human B cells from tonsil tissue and blood, enabling observation of antibody-secreting plasma cells in a controlled environment.

Georgia Tech and Vanderbilt University researchers built the human bone marrow-on-a-chip to study plasma cells in their native environment, addressing the challenge of accessing bone marrow tissue.

Two bone marrow niches play distinct but complementary roles: the perivascular niche supports recruitment and survival signaling, while the endosteal niche influences migration, persistence, and retention, together shaping plasma cell fate.

A notable finding is the stop-and-go migration of plasma cells, indicating they actively sample their surroundings rather than being stationary, which may be key to survival.

Funded by NIH and published in Science Advances, the study highlights the platform’s potential to test therapies for infection prevention, reducing autoimmunity, and controlling allergic responses.

The platform allows studying aging effects on plasma cells and examining autoimmunity and allergy using cells from diverse patient populations.

The system recreates two bone marrow subniches—the endosteal niche where plasma cells are stored and the perivascular niche where they proliferate and are activated—enabling detailed imaging and analysis.

The research challenges the notion of a uniform bone marrow environment and supports the idea that plasma cells seek specific supportive habitats, revealing a dynamic immune memory landscape.

The platform enables real-time manipulation and observation of the bone marrow environment, offering insights into vaccine durability, immune aging, autoimmune disease, chronic infection, blood cancers, and metastasis, and may explain why immunity wanes with age or why some vaccines confer longer protection.

Engineered lymphoid organoids contributed human antibody-secreting cells that preferentially migrated through the vascular network to accumulate around blood vessels, suggesting perivascular regions provide survival signals for long-term memory.

Researchers aim to answer how B cells relocate from lymph nodes to bone marrow to become long-lived plasma cells and how the bone marrow environment shapes responses to reinfection.