Plasma cell dynamics in the bone marrow niche

Cell Rep. 2021 Feb 9;34(6):108733. doi: 10.1016/j.celrep.2021.108733.

Abstract

Using intravital imaging, we report that bone marrow (BM) plasma cells (PCs) are motile. BM PCs exhibit a unique migration pattern, characterized by intermittent periods of high motility and longer stretches of confined migration or arrest. BM PCs accumulate into clusters, which have reduced cell motility. APRIL promotes cluster formation and overall PC motility in the BM. Although CXCL12 and its receptor, CXCR4, promote PC motility in the BM, VLA4 activity promotes arrest. However, blocking either pathway promotes PC egress from the BM. Under steady-state conditions, BM PCs recirculate to other bones and spleen. In older mice, overall PC motility and recirculation increase, and this is correlated with increased CXCR4 expression, which depends on PC age or maturation rather than mouse age. Altogether, these results suggest that changes in PC motility and CXCR4 expression are linked with survival of long-lived PCs in the BM.

Keywords: APRIL; CXCL12; CXCR4; VLA-4; antibody secreting cells; bone marrow; intravital imaging; migration; plasma cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism*
  • Cell Movement*
  • Cellular Microenvironment*
  • Chemokine CXCL12 / genetics
  • Chemokine CXCL12 / metabolism
  • Integrin alpha4beta1 / genetics
  • Integrin alpha4beta1 / metabolism
  • Mice
  • Mice, Transgenic
  • Plasma Cells / cytology
  • Plasma Cells / metabolism*
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / genetics
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / metabolism

Substances

  • CXCR4 protein, mouse
  • Chemokine CXCL12
  • Cxcl12 protein, mouse
  • Integrin alpha4beta1
  • Receptors, CXCR4
  • Tnfsf13 protein, mouse
  • Tumor Necrosis Factor Ligand Superfamily Member 13