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Publication : Identification of a negative regulatory role for spi-C in the murine B cell lineage.

First Author  Li SK Year  2015
Journal  J Immunol Volume  194
Issue  8 Pages  3798-807
PubMed ID  25769919 Mgi Jnum  J:308371
Mgi Id  MGI:6728885 Doi  10.4049/jimmunol.1402432
Citation  Li SK, et al. (2015) Identification of a negative regulatory role for spi-C in the murine B cell lineage. J Immunol 194(8):3798-807
abstractText  Spi-C is an E26 transformation-specific family transcription factor that is highly related to PU.1 and Spi-B. Spi-C is expressed in developing B cells, but its function in B cell development and function is not well characterized. To determine whether Spi-C functions as a negative regulator of Spi-B (encoded by Spib), mice were generated that were germline knockout for Spib and heterozygous for Spic (Spib(-/-)Spic(+/-)). Interestingly, loss of one Spic allele substantially rescued B cell frequencies and absolute numbers in Spib(-/-) mouse spleens. Spib(-/-)Spic(+/-) B cells had restored proliferation compared with Spib(-/-) B cells in response to anti-IgM or LPS stimulation. Investigation of a potential mechanism for the Spib(-/-)Spic(+/-) phenotype revealed that steady-state levels of Nfkb1, encoding p50, were elevated in Spib(-/-)Spic(+/-) B cells compared with Spib(-/-) B cells. Spi-B was shown to directly activate the Nfkb1 gene, whereas Spi-C was shown to repress this gene. These results indicate a novel role for Spi-C as a negative regulator of B cell development and function.
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