Switch circular DNA formed in cytokine-treated mouse splenocytes: evidence for intramolecular DNA deletion in immunoglobulin class switching

Cell. 1990 Jul 13;62(1):135-42. doi: 10.1016/0092-8674(90)90247-c.


We have characterized circular DNA in mouse splenocytes treated with the mitogen lipopolysaccharide (LPS) and various cytokines, including transforming growth factor beta (TGF-beta) and interleukin 4 (IL-4). Using probes of immunoglobulin heavy chain constant genes (CH), excision products of class switch recombination were identified. The majority of the clones contained the 3' portion of the switch mu (S mu) region and the 5' portion of other switch regions. Some clones contained 3'-S gamma sequences instead of 3'-S mu. This indicates that isotype switching may occur not only from C mu, but also from one of the C gamma genes to other CH genes further down-stream. In the presence of LPS, the cytokine TGF-beta enhanced the detection of 5'-S alpha-positive clones, while the lymphokine IL-4 enhanced 5'-S gamma 1 positives. The data support the notion that TGF-beta and IL-4 can direct isotype-specific class switching.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • Base Sequence
  • Biological Factors / pharmacology*
  • Chromosome Deletion*
  • Cytokines
  • DNA, Circular / drug effects
  • DNA, Circular / genetics*
  • DNA, Circular / isolation & purification
  • Female
  • Gene Library
  • Genes, Immunoglobulin*
  • Genes, Regulator*
  • Genes, Switch*
  • Immunoglobulin Heavy Chains / genetics*
  • Interferon-gamma / pharmacology
  • Interleukin-5 / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Restriction Mapping
  • Spleen / immunology
  • Transforming Growth Factors / pharmacology


  • Biological Factors
  • Cytokines
  • DNA, Circular
  • Immunoglobulin Heavy Chains
  • Interleukin-5
  • Transforming Growth Factors
  • Interferon-gamma

Associated data

  • GENBANK/M38071
  • GENBANK/M38072
  • GENBANK/M38073
  • GENBANK/M38074
  • GENBANK/M38075
  • GENBANK/M38076