Induction by anti-CD40 antibody or soluble CD40 ligand and cytokines of IgG, IgA and IgE production by B cells from patients with X-linked hyper IgM syndrome.
We studied the ability of B lymphocytes from patients with X-linked hyper IgM syndrome (HIGM1) to be activated via the CD40 membrane receptor. HIGM1 is caused by a CD40 ligand gene mutation, leading to defective expression on the membrane of activated T lymphocytes. We found that triggering of B cells by an anti-CD40 monoclonal antibody or the soluble CD40 ligand plus interleukin (IL)-4 or IL-10 led to B cell proliferation and/or differentiation towards IgG, IgA and IgE secretion. This was reflected by transcription of C gamma, alpha and epsilon membrane isotype expression and IgG, IgA and IgE production. These results confirm the integrity of B cells in patients with the HIGM1 immunodeficiency and open up new therapeutic possibilities.
Durandy
A
A
INSERM U 132, Hôpital des Enfants-Malades, Paris, France.
Schiff
C
C
Bonnefoy
J Y
JY
Forveille
M
M
Rousset
F
F
Mazzei
G
G
Milili
M
M
Fischer
A
A
D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D019013:CD40 Antigens; D023201:CD40 Ligand; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000494:pharmacology; D008040:Genetic Linkage; D006801:Humans; D006942:Hypergammaglobulinemia / Q000235:genetics / Q000276:immunology*; D007075:Immunoglobulin M / Q000032:analysis; D007136:Immunoglobulins / Q000096:biosynthesis*; D008024:Ligands; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D008969:Molecular Sequence Data; D014960:X Chromosome
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D016207:Cytokines; D007075:Immunoglobulin M; D007136:Immunoglobulins; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand