Direct evidence that gamma 1 and gamma 3 switching in human B cells is interleukin-10 dependent.
Interleukin-10 (IL-10) has various effects on B cell immunoglobulin (Ig) production. Indirect evidence suggests that IL-10 functions as a switch factor for IgG production. In this study, the switch deleted Ig gene DNA was isolated and characterized, as direct evidence that IL-10 induced isotype switching in human B cells. In addition, 16 chimeric Ig fragments were isolated, representing deleted DNA generated by in vitro isotype switching from mu to gamma in human B cells, following stimulation with IL-10 and anti-CD40 monoclonal antibodies (CD40 mAb). These clones consisted solely of S gamma 1/S mu and S gamma 3/S mu chimeric switch circular DNAs, no S gamma 2/S mu or S gamma 4/S mu switch DNA was observed. In addition, IL-10 alone induced only gamma 1 and gamma 3 germ-line mRNA transcripts, as determined by restriction digestion of the reverse transcription-polymerase chain reaction products. Three modes of mu-gamma 3 isotype switching were detected: (1) direct switching; (2) internal deletion of S mu proceeding mu to gamma 3 switching; and (3) internal deletion of S gamma 3 proceeding mu to gamma 3 switching. These results directly demonstrate that gamma 1 and gamma 3 switching in human B cells is specifically induced by IL-10 in the presence of CD40 mAb.
Fujieda
S
S
Hart and Louise Lyon Laboratory, Department of Medicine, Los Angeles, California, USA.
Saxon
A
A
Zhang
K
K
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D001483:Base Sequence; D019013:CD40 Antigens / Q000276:immunology; D002478:Cells, Cultured; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000187:drug effects; D005854:Germ Cells / Q000378:metabolism; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000187:drug effects; D007074:Immunoglobulin G / Q000235:genetics* / Q000378:metabolism; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000187:drug effects; D016753:Interleukin-10 / Q000502:physiology*; D015847:Interleukin-4 / Q000494:pharmacology; D008969:Molecular Sequence Data; D014066:Palatine Tonsil / Q000166:cytology; D011995:Recombination, Genetic / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D014158:Transcription, Genetic / Q000187:drug effects
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016753:Interleukin-10; D015847:Interleukin-4