Normal CD40-mediated activation of monocytes and dendritic cells from patients with hyper-IgM syndrome due to a CD40 pathway defect in B cells.
Patients with X-linked hyper-IgM syndrome [CD40 ligand (CD40L) deficiency] are prone to infections by intracellular parasites. It has been suggested that this susceptibility is caused by defective macrophage activation through the CD40L-CD40 pathway. We studied the CD40-mediated activation of monocytes and dendritic cells from patients affected with a CD40L+ hyper-IgM syndrome characterized by a defect of B lymphocyte responses to CD40 agonists. We show that the CD40-induced production of IL-6, IL-8 and TNF-alpha by monocytes, and IL-12 by dendritic cells, and expression of the activation markers CD83, the costimulatory molecules CD86 and CD80, and HLA-DR antigens were all similar in patient and control cells. This observation is consistent with the clinical characteristics of the syndrome: a defect of immunoglobulin switch but no susceptibility to opportunistic infections, as observed in CD40L-deficient patients. These observations suggest that CD40-mediated activation pathways could be, at least in part, different in B and monocytic/dendritic cell lineages.
Revy
P
P
Unité INSERM 429, Hôpital Necker-Enfants-Malades, Paris, France.
Geissmann
F
F
Debré
M
M
Fischer
A
A
Durandy
A
A
D015703:Antigens, CD; D001402:B-Lymphocytes / Q000502:physiology*; D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007075:Immunoglobulin M / Q000096:biosynthesis*; D007136:Immunoglobulins / Q000032:analysis; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D018664:Interleukin-12 / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000032:analysis / Q000172:deficiency*; D009000:Monocytes / Q000502:physiology*; D000097802:CD83 Antigen
D015703:Antigens, CD; D019013:CD40 Antigens; D023201:CD40 Ligand; D006684:HLA-DR Antigens; D007075:Immunoglobulin M; D007136:Immunoglobulins; D018664:Interleukin-12; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen