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

Authors

Stephen K.H. Li, Western University
Lauren A. Solomon, Western University
Patricia C. Fulkerson, Cincinnati Children's Hospital Medical Center
Rodney P. De Koter, Western UniversityFollow

Document Type

Article

Publication Date

4-15-2015

Journal

Journal of Immunology

Volume

194

Issue

8

First Page

3798

Last Page

3807

URL with Digital Object Identifier

10.4049/jimmunol.1402432

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.