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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2002-5-14
pubmed:abstractText
Ligation of B cell receptors (BCR) on immature B cells may induce apoptosis, while in mature B cells it stimulates cell activation and growth. The signaling pathway regulating the differential functional response, death or survival of the B cell is not fully characterized. We have tested the intracellular signaling requirement of these processes using B cells isolated from the spleen of irradiated auto-reconstituted (transitional immature B cells) and untreated mice (mature B cells), respectively. We compared the BCR induced intracellular [Ca2+] transient, protein tyrosine phosphorylation and ERK phosphorylation, furthermore, the activation of Elk-1 and CREB transcription factors. The BCR induced rise of intracellular [Ca2+] did not significantly differ in the two populations, only a slight difference in the late phase of the response was observed. Immature B cells responded with a maximum tyrosine phosphorylation to a five times lower dose of anti-IgM compared to the mature population. Most importantly, we have found a significant difference in the tyrosine phosphorylation of the Gab family adaptor proteins, Gab1/2. In contrast to mature B cells, crosslinking of BCR on immature B cells did not induce tyrosine phosphorylation of Gab2, thus the Gab2-organized signal amplification complex could not be produced. Furthermore, we detected a significant difference in the kinetics of BCR induced ERK, Elk-1 and CREB phosphorylation. In immature B cells, ERK was transiently phosphorylated, ceasing after 120 min, while in mature cells, ERK phosphorylation was sustained. Elk-1 and CREB activation was also transient in immature B cells, followed the kinetics of ERK phosphorylation. The lack of sustained Erk1/2 activation suppresses the transcription factors necessary for the proliferation signal. Since ERK is regulated by the phosphorylated Gab1/2, these data demonstrate that BCR triggered phosphorylation and signal amplification of Gab1/2 is a critical step in a life or death decision of B cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0165-2478
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
82
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
41-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12008033-Animals, pubmed-meshheading:12008033-Antigens, Differentiation, B-Lymphocyte, pubmed-meshheading:12008033-Apoptosis, pubmed-meshheading:12008033-B-Lymphocyte Subsets, pubmed-meshheading:12008033-B-Lymphocytes, pubmed-meshheading:12008033-Calcium, pubmed-meshheading:12008033-Cell Differentiation, pubmed-meshheading:12008033-Cells, Cultured, pubmed-meshheading:12008033-Kinetics, pubmed-meshheading:12008033-Lymphocyte Activation, pubmed-meshheading:12008033-Mice, pubmed-meshheading:12008033-Mice, Inbred BALB C, pubmed-meshheading:12008033-Mitogen-Activated Protein Kinases, pubmed-meshheading:12008033-Phosphoproteins, pubmed-meshheading:12008033-Phosphorylation, pubmed-meshheading:12008033-Receptors, Antigen, B-Cell, pubmed-meshheading:12008033-Signal Transduction, pubmed-meshheading:12008033-Spleen, pubmed-meshheading:12008033-Stem Cells, pubmed-meshheading:12008033-Transcription Factors
pubmed:year
2002
pubmed:articleTitle
BCR mediated signal transduction in immature and mature B cells.
pubmed:affiliation
Research Group of the Hungarian Academy of Sciences at the Department of Immunology, L. Eötvös University, Budapest, Hungary.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't