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Macrophages control the retention and trafficking of B lymphocytes in the splenic marginal zone

Mikael C I Karlsson1, Rodolphe Guinamard, Silvia Bolland

  • 1Laboratory of Molecular Genetics and Immunology, The Rockefeller University, Box 98, 1230 York Avenue, New York, NY 10021, USA.

The Journal of Experimental Medicine
|July 23, 2003
PubMed

Insights

SH2-containing inositol-5-phosphatase 1 (SHIP) disruption causes loss of marginal zone B cells by affecting macrophage retention. SHIP regulates Btk signaling, crucial for B cell interaction and splenic marginal zone organization.

Area of Science:

  • Immunology
  • Cell Biology
  • Spleen Microenvironment

Background:

  • The splenic marginal zone (MZ) harbors specialized B cells (MZBs) and macrophages (MZMOs).
  • SH2-containing inositol-5-phosphatase 1 (SHIP) plays a role in immune cell signaling.
  • Disruption of SHIP signaling impacts lymphocyte populations within the spleen.

Purpose of the Study:

  • To investigate the role of SHIP in regulating marginal zone B cell (MZB) and marginal zone macrophage (MZMO) interactions.
  • To identify molecular pathways involved in MZB retention and trafficking.
  • To elucidate the function of MZMOs in maintaining splenic architecture.

Main Methods:

  • Conditional depletion of SHIP in myeloid cells.
  • Genetic knockout models including SHIP/Bruton's tyrosine kinase (Btk) double knockout mice.
  • Analysis of B cell and macrophage populations and localization within the spleen.
  • Investigation of MARCO scavenger receptor interactions.

Main Results:

  • SHIP deficiency in myeloid cells leads to MZB loss and MZMO reorganization to the red pulp.
  • MZMOs are essential for MZB retention.
  • SHIP regulates the Btk activating pathway, influencing MZB homeostasis.
  • A direct interaction between MARCO on MZMOs and MZBs was identified, mediating MZB migration.
  • Staphylococcus aureus infection induced MZMO and MZB migration.

Conclusions:

  • SHIP is critical for maintaining splenic marginal zone structure by regulating macrophage function.
  • Macrophage-B cell interactions, particularly involving MARCO, are essential for B cell retention and trafficking.
  • The spleen's marginal zone is a dynamic environment regulated by specific cellular crosstalk.

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