Continued RAG expression in late stages of B cell development and no apparent re-induction after immunization
- PMID: 10458165
- DOI: 10.1038/23287
Continued RAG expression in late stages of B cell development and no apparent re-induction after immunization
Abstract
Models of B-cell development in the immune system suggest that only those immature B cells in the bone marrow that undergo receptor editing express V(D)J-recombination-activating genes (RAGs). Here we investigate the regulation of RAG expression in transgenic mice carrying a bacterial artificial chromosome that encodes a green fluorescent protein reporter instead of RAG2. We find that the reporter is expressed in all immature B cells in the bone marrow and spleen. Endogenous RAG messenger RNA is expressed in immature B cells in bone marrow and spleen and decreases by two orders of magnitude as they acquire higher levels of surface immunoglobulin M (IgM). Once RAG expression is stopped it is not re-induced during immune responses. Our findings may help to reconcile a series of apparently contradictory observations, and suggest a new model for the mechanisms that regulate allelic exclusion, receptor editing and tolerance.
Comment in
-
Developing B-cell theories.Nature. 1999 Aug 12;400(6745):614-5, 617. doi: 10.1038/23134. Nature. 1999. PMID: 10458155 No abstract available.
Similar articles
-
Peripheral expression of RAG in human B lymphocytes in normal and pathological conditions is dependent on interleukin-6.Autoimmun Rev. 2007 Jun;6(6):415-20. doi: 10.1016/j.autrev.2007.01.002. Epub 2007 Feb 2. Autoimmun Rev. 2007. PMID: 17537388 Review.
-
Variegated transcriptional activation of the immunoglobulin kappa locus in pre-b cells contributes to the allelic exclusion of light-chain expression.Cell. 2004 Jul 9;118(1):19-29. doi: 10.1016/j.cell.2004.06.019. Cell. 2004. PMID: 15242641
-
Central and peripheral RAG protein re-expression: underestimate mechanisms of tolerance?Scand J Immunol. 2006 Sep;64(3):185-9. doi: 10.1111/j.1365-3083.2006.01801.x. Scand J Immunol. 2006. PMID: 16918685 Review.
-
Developing B-cell theories.Nature. 1999 Aug 12;400(6745):614-5, 617. doi: 10.1038/23134. Nature. 1999. PMID: 10458155 No abstract available.
-
Characterization of B cells expressing recombination activating genes in germinal centers of immunized mouse lymph nodes.J Immunol. 1997 Mar 15;158(6):2509-12. J Immunol. 1997. PMID: 9058779
Cited by
-
Phosphorothioate-modified CpG oligodeoxynucleotides mimic autoantigens and reveal a potential role for Toll-like receptor 9 in receptor revision.Immunology. 2013 Jun;139(2):166-78. doi: 10.1111/imm.12063. Immunology. 2013. PMID: 23289794 Free PMC article.
-
Retinoic acid hypersensitivity promotes peripheral tolerance in recent thymic emigrants.J Immunol. 2013 Mar 15;190(6):2603-13. doi: 10.4049/jimmunol.1200852. Epub 2013 Feb 11. J Immunol. 2013. PMID: 23401586 Free PMC article.
-
Novel molecular mechanism for generating NK-cell fitness and memory.Eur J Immunol. 2015 Jul;45(7):1906-15. doi: 10.1002/eji.201445339. Epub 2015 Jun 24. Eur J Immunol. 2015. PMID: 26018782 Free PMC article. Review.
-
Analysis of naïve lung CD4 T cells provides evidence of functional lung to lymph node migration.Proc Natl Acad Sci U S A. 2013 Jan 29;110(5):1821-6. doi: 10.1073/pnas.1221306110. Epub 2013 Jan 14. Proc Natl Acad Sci U S A. 2013. PMID: 23319636 Free PMC article.
-
Cancer co-opts differentiation of B-cell precursors into macrophage-like cells.Nat Commun. 2022 Sep 14;13(1):5376. doi: 10.1038/s41467-022-33117-y. Nat Commun. 2022. PMID: 36104343 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Research Materials
