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NF-B activity marks cells engaged in receptor editing

¹ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720
² Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892

CORRESPONDENCE Mark S. Schlissel: mss{at}berkeley.edu

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-B–dependent IB gene was replaced with a lacZ (β-gal) reporter complementary DNA (cDNA; IB^+/lacZ) suggests a potential role for NF-B in receptor editing. Sorted β-gal⁺ pre–B cells showed increased levels of various markers of receptor editing. In IB^+/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 IB superrepressor in primary bone marrow cultures resulted in diminished germline and rearranged 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-B and is required for receptor editing, we suggest that NF-B could be acting through IRF4 to regulate receptor editing.

Abbreviations used: β-gal, β-galactosidase; BCR, B cell receptor; cDNA, complementary DNA; FDG, fluorescein di-β-D-galactopyranoside; HPRT, hypoxanthine-guanine phosphoribosyl transferase; IgHC, Ig heavy chain; IgLC, Ig light chain; LM-PCR, ligation-mediated PCR; mRNA, messenger RNA; RPS3, ribosomal protein S3; RSS, recombination signal sequence.

© 2009 Cadera et al.
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