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BCR Signaling in Transitional versus Mature B cells
Author(s) -
Andrews Sarah F,
Rawlings David J
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.662.23
Subject(s) - breakpoint cluster region , nf κb , phosphorylation , downregulation and upregulation , microbiology and biotechnology , iκbα , transcription factor , b cell receptor , biology , b cell , signal transduction , iκb kinase , chemistry , cancer research , immunology , gene , antibody , genetics
Early transitional (T1) splenic B cells, in contrast to follicular mature (FM) B cells, apoptose and fail to proliferate in response to BCR engagement. Consistent with these distinct responses, NFκB target genes, essential for proliferation and survival, are rapidly upregulated in FM but not in T1 B cells upon BCR engagement. Previous studies have implied that proximal signals required to mediate IKK activation are dysfunctional in immature B cells. We directly evaluated this hypothesis using highly purified T1 vs. FM splenic B cells closely matched for surface IgM expression. Surprisingly, key proximal signals required for NFκB activation, including PI3K, PLCγ2, and PKCβ activation, are intact in early transitional B cells. When we measured the BCR‐triggered, canonical NFκB signaling cascade in T1 vs. FM B cells we saw equivalent levels of IKKα/β phosphorylation, IκBα degradation, and nuclear translocation of c‐Rel and RelA. Taken together, our data strongly indicate that proximal NFκB signaling is fully activated in T1 B cells. In addition, studies using chromatin IPs suggest that the failure to upregulate NFκB target genes is due to an altered capacity to mediate NFκB transcription at the nuclear level. These studies provide important insight into what controls cell fate upon BCR engagement in peripheral B cell subsets. Funded by NIH 5R01HD37091.