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Automated Quantification of Hematopoietic Cell – Stromal Cell Interactions in Histological Images of Undecalcified Bone
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Plasma cell dynamics in the bone marrow niche

Zachary Benet1, Zhixin Jing1, David R Fooksman1

  • 1Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Cell Reports
|February 10, 2021
PubMed

Insights

Bone marrow plasma cells (PCs) are motile and form clusters. Their movement and survival in the bone marrow are regulated by specific molecular pathways, influencing their recirculation.

Area of Science:

  • Immunology
  • Cell Biology
  • Hematology

Background:

  • Plasma cells (PCs) reside in the bone marrow (BM), but their dynamic behavior and regulation within this niche are not fully understood.
  • Understanding PC migration is crucial for comprehending humoral immunity and long-lived plasma cell survival.

Purpose of the Study:

  • To investigate the motility patterns of bone marrow plasma cells (BM PCs) using intravital imaging.
  • To identify molecular factors and pathways that regulate BM PC motility, clustering, and egress.
  • To explore the relationship between PC motility, CXCR4 expression, and PC survival in aging mice.

Main Methods:

  • Intravital imaging of bone marrow in live mice.
  • Pharmacological inhibition of specific molecular pathways (e.g., CXCL12/CXCR4, VLA4).
  • Analysis of plasma cell clustering, motility, and recirculation patterns.

Main Results:

  • Bone marrow plasma cells (PCs) exhibit unique, intermittent motility patterns and form clusters with reduced motility.
  • APRIL enhances PC motility and cluster formation, while CXCL12/CXCR4 signaling promotes motility and VLA4 promotes arrest.
  • Inhibition of either CXCL12/CXCR4 or VLA4 pathways enhances PC egress from the BM.
  • PC motility and recirculation increase in older mice, correlating with elevated CXCR4 expression dependent on PC age, not mouse age.

Conclusions:

  • BM PCs are motile and their migration is tightly regulated by distinct molecular cues.
  • Modulating PC motility and CXCR4 expression impacts their survival and localization within the BM niche.
  • These findings provide insights into the dynamics of long-lived plasma cells and their potential role in immune memory.
Keywords:
APRILCXCL12CXCR4VLA-4antibody secreting cellsbone marrowintravital imagingmigrationplasma cells

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