The Role of CD40/CD40 Ligand Interactions in Bone Marrow Granulopoiesis

Figure 1

Schematic diagram of the CD40/CD40L interactions in the bone marrow. Under steady state conditions, CD40 is minimally expressed on the BM granulocytic progenitor cells, but it is constitutively expressed on BM stromal cells, and upon ligation with CD40 ligand (CD40L), it induces the production of FMS-like tyrosine kinase 3 ligand (Flt3-L), granulocyte-colony-stimulating factor (G-CSF), and granulocyte/monocyte-colony-stimulating factor (GM-CSF). Under inflammatory conditions, involving increased tumour necrosis factor-α (TNFα), Fas ligand (FasL), and CD40L production, as found in the BM microenvironment of chronic idiopathic neutropenia (CIN) patients, CD40 expression is upregulated in all stages of the granulocytic differentiation, and upon activation with CD40L, it induces the apoptotic cell death both directly and indirectly through Fas upmodulation, counterbalancing the beneficial effect of G-CSF and GM-CSF produced by BM stromal cells.