NIH reported that a scientific team has engineered a laboratory model to observe how antibody-producing plasma cells migrate, mature, and survive inside human bone marrow. The findings, published in Science Advances, introduce a platform that pairs a lymph node-mimicking organoid with a microfluidic tissue chip to examine immune processes that have been difficult to observe in living human tissue.
Plasma cells protect the body by generating antibodies against infections, but improper antibody production can trigger autoimmune diseases and allergies, while runaway cell proliferation can cause blood cancer. Long-lived plasma cells in bone marrow sustain long-term immunity following vaccination or illness. Scientists have struggled to track how those cells move into the bone marrow and persist over time.
Ankur Singh led the team at Georgia Tech that built the lymphoid organoid. The researchers isolated B cells from human blood and tonsil tissue, culturing them in an artificial microenvironment mimicking lymphoid tissue. Singh's team used inactivated influenza virus to stimulate the B cells into becoming antibody-secreting plasma cells, producing enough cells to run experiments in the tissue chip.
Device architecture
Krishnendu Roy’s laboratory at Vanderbilt University engineered the bone marrow chip using a microfluidic vascularized environment. The researchers built the model inside a three-by-five-inch stack of 96-well plastic plates, each measuring less than half an inch thick. Channels crisscross the chip interior, lined with a gel-like material that mimics bone marrow tissue and carries nutrients and growth factors to sustain the cells.
The chip replicates two distinct internal zones. An outer layer models the endosteal subniche, where plasma cells rest until needed by the immune system. A deeper inner zone models the perivascular subniche, which surrounds a network of blood vessels where plasma cells activate and multiply.
Imaging and applications
Singh noted that high-resolution imaging of plasma cells inside living human bone marrow is nearly impossible, leaving researchers dependent on mouse models. The new chip allows direct imaging of cell activity in response to signaling proteins and lets scientists evaluate how different biological niches affect cell durability.
Researchers can seed the system with cells from specific patient groups to examine how aging, allergic disorders, and autoimmune conditions affect plasma cell behavior. The team noted that they still want to resolve why B cells display a stop-and-go movement pattern and whether that movement represents continuous migration through bone marrow tissue.
NIAID supported the research under grants R01AI186314 and R01AI181282, with additional funding from NIGMS grant T32GM145735.
