Interleukin-10 induces immunoglobulin G isotype switch recombination in human CD40-activated naive B lymphocytes.
Upon activation, B lymphocytes can change the isotype of the antibody they express by immunoglobulin (Ig) isotype switch recombination. In previous studies on the regulation of human IgG expression, we demonstrated that interleukin 10 (IL-10) could stimulate IgG1 and IgG3 secretion by human CD40-activated naive (sIgD+) tonsillar B cells. To assess whether IL-10 actually promotes the DNA recombination underlying switching to these isotypes, we examined the effect of IL-10 on the generation of reciprocal products that form DNA circles as by-products of switch recombination. The content of reciprocal products characteristic of mu-gamma recombination was elevated after culture of CD40-activated tonsillar sIgD+ B cells with either IL-4 or IL-10, although high levels of IgG secretion were observed only with IL-10. Unlike IL-4, IL-10 did not induce reciprocal products of mu-epsilon and gamma-epsilon switch recombination. These results demonstrate that IL-10 promotes both switching to gamma and IgG secretion.
Malisan
F
F
Schering-Plough, Laboratory for Immunological Research, Dardilly, France.
Brière
F
F
Bridon
J M
JM
Harindranath
N
N
Mills
F C
FC
Max
E E
EE
Banchereau
J
J
Martinez-Valdez
H
H
D015703:Antigens, CD / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D001483:Base Sequence; D019013:CD40 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D017931:DNA Primers; D005803:Genes, Immunoglobulin; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000235:genetics; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis* / Q000235:genetics; D007134:Immunoglobulin Switch Region; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid
D015703:Antigens, CD; D019013:CD40 Antigens; D017931:DNA Primers; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D016753:Interleukin-10; D015847:Interleukin-4