Direct evidence that gamma 1 and gamma 3 switching in human B cells is interleukin-10 dependent

Mol Immunol. 1996 Dec;33(17-18):1335-43. doi: 10.1016/s0161-5890(96)00092-2.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism*
  • Base Sequence
  • CD40 Antigens / immunology
  • Cells, Cultured
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain / drug effects
  • Germ Cells / metabolism
  • Humans
  • Immunoglobulin Class Switching* / drug effects
  • Immunoglobulin G / genetics*
  • Immunoglobulin G / metabolism
  • Immunoglobulin M / biosynthesis
  • Immunoglobulin M / drug effects
  • Interleukin-10 / physiology*
  • Interleukin-4 / pharmacology
  • Molecular Sequence Data
  • Palatine Tonsil / cytology
  • Recombination, Genetic / immunology
  • Signal Transduction / immunology
  • Transcription, Genetic / drug effects

Substances

  • Antibodies, Monoclonal
  • CD40 Antigens
  • Immunoglobulin G
  • Immunoglobulin M
  • Interleukin-10
  • Interleukin-4