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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1996-12-10
pubmed:abstractText
We have developed an efficient in vitro class switching system using a subclone (CH12F3) of the IgM+ CH12.LX lymphoma cell line. CH12F3 cells switched from surface IgM+ cells to surface IgA+ cells at a high frequency (50%) after 72 h stimulation with IL-4, transforming growth factor (TGF)-beta and CD40L. No other class isotype-producing cells were detected, indicating that the CH12F3 clone is exclusively committed to IgA isotype switching. To understand the molecular basis of the isotype commitment, we studied the methylation profiles of I region promoters and I region transcription of CH12F3 cells. No germline transcripts other than those from the I alpha region were detected and only the I alpha promoter was demethylated in uninduced CH12F3 cells. TGF-beta, CD40L and IL-4 synergistically induced efficient switch recombination in CH12F3 cells, suggesting that the three stimulations up-regulate different steps of switch recombination in isotype-committed B cells such as CH12F3 cells. Stimulation of CH12F3 cells by IL-4 or TGF-beta, but not by CD40L, induced transient but complete methylation of the I alpha region. TGF-beta and CD40L, but not IL-4, increased the amounts of germline alpha transcripts. We found that the extents of methylation and the amounts of germline transcripts do not necessarily correlate with the efficiency of recombination in induced CH12F3 cells. These results led to the proposal that switch recombination can be separated into at least two phases, i.e. commitment and recombination. The roles of IL-4, TGF-beta and CD40L in the two phases are discussed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0953-8178
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
193-201
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed-meshheading:8671604-Animals, pubmed-meshheading:8671604-Antigens, CD40, pubmed-meshheading:8671604-B-Lymphocytes, pubmed-meshheading:8671604-CD40 Ligand, pubmed-meshheading:8671604-Cell Separation, pubmed-meshheading:8671604-Clone Cells, pubmed-meshheading:8671604-DNA Methylation, pubmed-meshheading:8671604-Female, pubmed-meshheading:8671604-Immunoglobulin A, pubmed-meshheading:8671604-Immunoglobulin Class Switching, pubmed-meshheading:8671604-Immunoglobulin M, pubmed-meshheading:8671604-Interleukin-4, pubmed-meshheading:8671604-Ligands, pubmed-meshheading:8671604-Lymphocyte Activation, pubmed-meshheading:8671604-Lymphoma, B-Cell, pubmed-meshheading:8671604-Membrane Glycoproteins, pubmed-meshheading:8671604-Mice, pubmed-meshheading:8671604-Transcription, Genetic, pubmed-meshheading:8671604-Transforming Growth Factor beta, pubmed-meshheading:8671604-Tumor Cells, Cultured
pubmed:year
1996
pubmed:articleTitle
High frequency class switching of an IgM+ B lymphoma clone CH12F3 to IgA+ cells.
pubmed:affiliation
Center for Molecular Biology and Genetics, Kyoto University, Jaspan.
pubmed:publicationType
Journal Article