Ikaros controls isotype selection during immunoglobulin class switch recombination. - Archive ouverte HAL Access content directly
Journal Articles Journal of Experimental Medicine Year : 2009

Ikaros controls isotype selection during immunoglobulin class switch recombination.

(1) , (1) , (1) , (1)
1

Abstract

Class switch recombination (CSR) allows the humoral immune response to exploit different effector pathways through specific secondary antibody isotypes. However, the molecular mechanisms and factors that control immunoglobulin (Ig) isotype choice for CSR are unclear. We report that deficiency for the Ikaros transcription factor results in increased and ectopic CSR to IgG(2b) and IgG(2a), and reduced CSR to all other isotypes, regardless of stimulation. Ikaros suppresses active chromatin marks, transcription, and activation-induced cytidine deaminase (AID) accessibility at the gamma2b and gamma2a genes to inhibit class switching to these isotypes. Further, Ikaros directly regulates isotype gene transcription as it directly binds the Igh 3' enhancer and interacts with isotype gene promoters. Finally, Ikaros-mediated repression of gamma2b and gamma2a transcription promotes switching to other isotype genes by allowing them to compete for AID-mediated recombination at the single-cell level. Thus, our results reveal transcriptional competition between constant region genes in individual cells to be a critical and general mechanism for isotype specification during CSR. We show that Ikaros is a master regulator of this competition.

Dates and versions

inserm-00387911 , version 1 (26-05-2009)

Identifiers

Cite

Maclean Sellars, Bernardo Reina-San-Martin, Philippe Kastner, Susan Chan. Ikaros controls isotype selection during immunoglobulin class switch recombination.. Journal of Experimental Medicine, 2009, 206 (5), pp.1073-87. ⟨10.1084/jem.20082311⟩. ⟨inserm-00387911⟩
50 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More