NF-κB activity marks cells engaged in receptor editing

Emily J. Cadera, Fengyi Wan, Rupesh H. Amin, Hector Nolla, Michael J. Lenardo, Mark S. Schlissel

Research output: Contribution to journalArticle

Abstract

Because of the extreme diversity in immunoglobulin genes, tolerance mechanisms are necessary to ensure that B cells do not respond to self-antigens. One such tolerance mechanism is called receptor editing. If the B cell receptor (BCR) on an immature B cell recognizes self-antigen, it is down-regulated from the cell surface, and light chain gene rearrangement continues in an attempt to edit the autoreactive specificity. Analysis of a heterozygous mutant mouse in which the NF-κB-dependent IκBα gene was replaced with a lacZ (β-gal) reporter complementary DNA (cDNA; IκBα +/lacZ) suggests a potential role for NF-κB in receptor editing. Sorted β-gal+ pre-B cells showed increased levels of various markers of receptor editing. In IκBα+/lacZ reporter mice expressing either innocuous or self-specific knocked in BCRs, β-gal was preferentially expressed in pre-B cells from the mice with self-specific BCRs. Retroviral-mediated expression of a cDNA encoding an IκBα superrepressor in primary bone marrow cultures resulted in diminished germline κ and rearranged λ transcripts but similar levels of RAG expression as compared with controls. We found that IRF4 transcripts were up-regulated in β-gal+ pre-B cells. Because IRF4 is a target of NF-κB and is required for receptor editing, we suggest that NF-κB could be acting through IRF4 to regulate receptor editing.

Original languageEnglish (US)
Pages (from-to)1803-1816
Number of pages14
JournalJournal of Experimental Medicine
Volume206
Issue number8
DOIs
StatePublished - Aug 3 2009
Externally publishedYes

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B-Lymphoid Precursor Cells
Complementary DNA
Autoantigens
B-Lymphocytes
Immunoglobulin Genes
Gene Rearrangement
Bone Marrow
Light
Genes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Medicine(all)

Cite this

Cadera, E. J., Wan, F., Amin, R. H., Nolla, H., Lenardo, M. J., & Schlissel, M. S. (2009). NF-κB activity marks cells engaged in receptor editing. Journal of Experimental Medicine, 206(8), 1803-1816. https://doi.org/10.1084/jem.20082815

NF-κB activity marks cells engaged in receptor editing. / Cadera, Emily J.; Wan, Fengyi; Amin, Rupesh H.; Nolla, Hector; Lenardo, Michael J.; Schlissel, Mark S.

In: Journal of Experimental Medicine, Vol. 206, No. 8, 03.08.2009, p. 1803-1816.

Research output: Contribution to journalArticle

Cadera, EJ, Wan, F, Amin, RH, Nolla, H, Lenardo, MJ & Schlissel, MS 2009, 'NF-κB activity marks cells engaged in receptor editing', Journal of Experimental Medicine, vol. 206, no. 8, pp. 1803-1816. https://doi.org/10.1084/jem.20082815
Cadera EJ, Wan F, Amin RH, Nolla H, Lenardo MJ, Schlissel MS. NF-κB activity marks cells engaged in receptor editing. Journal of Experimental Medicine. 2009 Aug 3;206(8):1803-1816. https://doi.org/10.1084/jem.20082815
Cadera, Emily J. ; Wan, Fengyi ; Amin, Rupesh H. ; Nolla, Hector ; Lenardo, Michael J. ; Schlissel, Mark S. / NF-κB activity marks cells engaged in receptor editing. In: Journal of Experimental Medicine. 2009 ; Vol. 206, No. 8. pp. 1803-1816.
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