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

The Journal of Immunology : Official Journal of the American Association of Immunologists
Stephen K H LiRodney P DeKoter

Abstract

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.

References

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Aug 5, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Brock L SchweitzerRodney P DeKoter
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Nov 9, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rodney P DeKoterLee Ann Garrett-Sinha
Sep 8, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Li S XuRodney P DeKoter
Jan 30, 2014·Annual Review of Immunology·Ellen V Rothenberg

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Citations

Feb 3, 2016·The Journal of Experimental Medicine·Jeffrey J BednarskiBarry P Sleckman
Aug 1, 2018·Proceedings of the National Academy of Sciences of the United States of America·Hisako KayamaKiyoshi Takeda
Nov 13, 2020·Nucleic Acids Research·Clarissa S SantosoJuan I Fuxman Bass

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