Linked Life Data

8046237

Source:http://linkedlifedata.com/resource/pubmed/id/8046237

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1994-9-1
pubmed:abstractText
The membrane-associated form of Ig heavy chain (mu) protein has been implicated as a critical regulator of B cell development. Mutant mice unable to produce the membrane form of mu protein fail to produce mature B cells. Splenic B cells from mice transgenic for a functionally rearranged Ig mu gene show a marked decrease in endogenous heavy chain gene rearrangement. We have analyzed the effects of a human mu transgene on the regulation of V(D)J recombination during B cell development in the mouse fetal liver. We found that mu transgenic and wild-type littermate mice begin kappa light chain gene rearrangement at the same time during development but the transgenic mice show a striking increase in the frequency of kappa gene rearrangement. The transgenic mice also show an increase in the levels of a germ-line kappa gene transcript known to be associated with kappa gene rearrangement. D-to-JH heavy chain gene rearrangement is unaffected throughout development by the presence of the mu transgene. Endogenous heavy chain gene V-to-DJH rearrangement occurs with similar frequency in transgenic and nontransgenic fetal livers during midgestation but is reduced in late gestation mu transgenic fetal liver. We show that this decrease in rearrangement is associated with a decrease in unrearranged VH gene transcription. Furthermore, we show that changes in the frequencies of rearranged kappa and mu genes are accompanied by changes in the frequencies of dsDNA breaks, a V(D)J recombination reaction intermediate associated with each of these loci. We propose that membrane-associated mu protein regulates B cell development by signaling a change in the pattern of unrearranged Ig gene transcriptional activity, thereby retargeting the V(D)J recombinase.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
153
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1645-57
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:8046237-Alleles, pubmed-meshheading:8046237-Animals, pubmed-meshheading:8046237-B-Lymphocytes, pubmed-meshheading:8046237-Base Sequence, pubmed-meshheading:8046237-Cell Differentiation, pubmed-meshheading:8046237-DNA Primers, pubmed-meshheading:8046237-Female, pubmed-meshheading:8046237-Gene Expression Regulation, pubmed-meshheading:8046237-Gene Rearrangement, B-Lymphocyte, pubmed-meshheading:8046237-Genes, Immunoglobulin, pubmed-meshheading:8046237-Gestational Age, pubmed-meshheading:8046237-Immunoglobulin Heavy Chains, pubmed-meshheading:8046237-Immunoglobulin kappa-Chains, pubmed-meshheading:8046237-Immunoglobulin mu-Chains, pubmed-meshheading:8046237-Liver, pubmed-meshheading:8046237-Male, pubmed-meshheading:8046237-Mice, pubmed-meshheading:8046237-Mice, Inbred BALB C, pubmed-meshheading:8046237-Mice, Transgenic, pubmed-meshheading:8046237-Molecular Sequence Data, pubmed-meshheading:8046237-RNA, Messenger, pubmed-meshheading:8046237-Transcription, Genetic
pubmed:year
1994
pubmed:articleTitle
Ig heavy chain protein controls B cell development by regulating germ-line transcription and retargeting V(D)J recombination.
pubmed:affiliation
Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD 21205.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't