Attenuation of IL-7 receptor signaling is not required for allelic exclusion

The Journal of Immunology : Official Journal of the American Association of Immunologists
Wynette M WillMichael A Farrar

Abstract

Allelic exclusion prevents pre-B cells from generating more than one functional H chain, thereby ensuring the formation of a unique pre-BCR. The signaling processes underlying allelic exclusion are not clearly understood. IL-7R-dependent signals have been clearly shown to regulate the accessibility of the Ig H chain locus. More recent work has suggested that pre-BCR-dependent attenuation of IL-7R signaling returns the H chain loci to an inaccessible state; this process has been proposed to underlie allelic exclusion. Importantly, this model predicts that preventing pre-BCR-dependent down-regulation of IL-7R signaling should interfere with allelic exclusion. To test this hypothesis, we made use of transgenic mice that express a constitutively active form of STAT5b (STAT5b-CA). STAT5b-CA expression restores V(D)J recombination in IL-7R(-/-) B cells, demonstrating that IL-7 regulates H chain locus accessibility and V(D)J recombination via STAT5 activation. To examine the effects of constitutively active STAT5b on allelic exclusion, we crossed STAT5b-CA mice (which express the IgM(b) allotype) to IgM(a) allotype congenic mice. We found no difference in the percentage of IgM(a)/IgM(b)-coexpressing B cells in STAT5b-CA vs littermate ...Continue Reading

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Nov 25, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Matthew A BurchillMichael A Farrar
Mar 23, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·C Justin Van De WieleT Kent Teague
Apr 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christine A GoetzMichael A Farrar
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Citations

Dec 22, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Matthew A BurchillMichael A Farrar
Dec 7, 2007·The Journal of Experimental Medicine·Jamie Geier BatesMark S Schlissel
Jan 27, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Suchita HodawadekarMichael L Atchison
May 15, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kristen JohnsonJane A Skok
Jan 13, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lin-Xi LiMichael A Farrar

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