Replacement of I¿3 germ-line promoter by I¿1 inhibits class-switch recombination to IgG3

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 104; no. 51; p. 20484
• Main Authors: Oruc, Zeliha, Boumediene, Ahmed, Bert, Marc Le, Khamlichi, Ahmed Amine
• Format: Journal Article
• Language: English
• Published: Washington National Academy of Sciences 18-12-2007
• Subjects: Gene loci; Immunoglobulins; Rodents
• ISSN: 0027-8424; 1091-6490

Class-switch recombination (CSR) enables IgM-producing B cells to switch to the production of IgG, IgE, and IgA. The process requires germ-line (GL) transcription that initiates from promoters upstream of switch (S) sequences and is regulated by the 3' regulatory region (3'RR) located downstream of the Ig heavy chain (IgH) locus. How the 3'RR effect its long-range activation is presently unclear. We generated a mouse line in which I...3 GL promoter was replaced by I...1. We found that GL transcription could initiate from the inserted I...1 promoter and was induced by increased concentrations of IL-4 and that the transcripts were normally spliced. However, when compared with OL transcripts derived from the endogenous I...1 promoter in the same stimulation conditions, those from the inserted I...1 promoter were less abundant. CSR to C...3 was abrogated both in vivo and in vitro. The results strongly suggest that the endogenous Ill promoter insulates the inserted I...1 from the long-range activating effect of the 3'RR. The implications of our findings are discussed in light of the prominent models of long-distance activation in complex loci. (ProQuest: ... denotes formulae/symbols omitted.)