Cutting Edge: The Tetraspanin CD53 Promotes CXCR4 Signaling and Bone Marrow Homing in B Cells

J Immunol. 2024 Apr 1;212(7):1075-1080. doi: 10.4049/jimmunol.2300336.

Abstract

B cell trafficking involves the coordinated activity of multiple adhesive and cytokine-receptor interactions, and the players in this process are not fully understood. In this study, we identified the tetraspanin CD53 as a critical regulator of both normal and malignant B cell trafficking. CXCL12 is a key chemokine in B cell homing to the bone marrow and secondary lymphoid organs, and both normal and malignant B cells from Cd53-/- mice have reduced migration toward CXCL12 in vitro, as well as impaired marrow homing in vivo. Using proximity ligation studies, we identified the CXCL12 receptor, CXCR4, as a novel, to our knowledge, CD53 binding partner. This interaction promotes receptor function, because Cd53-/- B cells display reduced signaling and internalization of CXCR4 in response to CXCL12. Together, our data suggest that CD53 interacts with CXCR4 on both normal and malignant B cells to promote CXCL12 signaling, receptor internalization, and marrow homing.

MeSH terms

  • Animals
  • B-Lymphocytes* / metabolism
  • Bone Marrow Cells / metabolism
  • Bone Marrow* / metabolism
  • Carrier Proteins / metabolism
  • Cell Movement / physiology
  • Chemokine CXCL12 / metabolism
  • Mice
  • Receptors, CXCR4 / metabolism
  • Signal Transduction
  • Tetraspanins / metabolism

Substances

  • Chemokine CXCL12
  • Tetraspanins
  • Carrier Proteins
  • Receptors, CXCR4