Macrophages and stromal cells phagocytose apoptotic bone marrow-derived B lineage cells

Area of Science:

• Immunology
• Cell Biology
• Hematopoiesis

Background:

• Macrophages are hypothesized to clear B cell precursors undergoing apoptosis due to nonproductive immunoglobulin (Ig) gene rearrangements in the bone marrow.
• Previous evidence relied on micrographs showing macrophage association with apoptotic B lineage cells, lacking functional data on phagocytosis and receptor identification.

Purpose of the Study:

• To provide functional evidence for macrophage-mediated phagocytosis of apoptotic B cell precursors.
• To identify the specific receptors involved in this phagocytic process.
• To explore the role of the hemopoietic microenvironment, specifically bone marrow stromal cells, in apoptotic cell clearance.

Main Methods:

• Isolation of macrophages from murine bone marrow.
• Incubation of macrophages with apoptotic murine B lineage cells.
• Identification of phagocytic receptors using molecular and cellular assays.
• Assessment of apoptotic cell clearance by murine bone marrow stromal cells.

Main Results:

• Murine bone marrow macrophages efficiently phagocytose apoptotic murine B lineage cells.
• Multiple receptors, including CD14, integrins, class A scavenger receptor, and CD31 (PECAM-1), mediate this phagocytosis.
• Murine bone marrow stromal cells also clear apoptotic cells through an integrin-dependent mechanism.

Conclusions:

• Macrophages play a significant functional role in clearing apoptotic B cell precursors from the bone marrow.
• Specific receptors mediate the phagocytosis of apoptotic B lineage cells by macrophages.
• Bone marrow stromal cells contribute to apoptotic cell clearance, indicating a broader role for the hemopoietic microenvironment in B cell development.