Cross talk between immunoglobulin heavy-chain transcription and RNA surveillance during B cell development.

Aurélien Tinguely, Guillaume Chemin, Sophie Péron, Christophe Sirac, Stéphane Reynaud, Michel Cogné, Laurent Delpy

Université de Limoges, CNRS UMR 6101, Limoges, France.

Molecular and cellular biology 2012 Jan

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Immunoglobulin (Ig) genes naturally acquire frequent premature termination codons during the error-prone V(D)J recombination process. Although B cell differentiation is linked to the expression of productive Ig alleles, the transcriptional status of nonfunctionally recombined alleles remains unclear. Here, we tracked transcription and posttranscriptional regulation for both Ig heavy-chain (IgH) alleles in mice carrying a nonfunctional knock-in allele. We show that productively and nonproductively VDJ-rearranged alleles are transcribed throughout B cell development, carry similar active chromatin marks, and even display equivalent RNA polymerase II (RNAPII) loading after B cell stimulation. Hence, these results challenge the idea that the repositioning of one allele to heterochromatin could promote the silencing of nonproductive alleles. Interestingly, the efficiency of downstream RNA surveillance mechanisms fluctuates according to B cell activation and terminal differentiation: unspliced nonfunctional transcripts accumulate in primary B cells, while B cell activation promotes IgH transcription, RNA splicing, and nonsense-mediated mRNA decay (NMD). Altogether, IgH transcription and RNA splicing rates determine by which RNA surveillance mechanisms a B cell can get rid of nonproductive IgH mRNAs.

Citation

Aurélien Tinguely, Guillaume Chemin, Sophie Péron, Christophe Sirac, Stéphane Reynaud, Michel Cogné, Laurent Delpy. Cross talk between immunoglobulin heavy-chain transcription and RNA surveillance during B cell development. Molecular and cellular biology. 2012 Jan;32(1):107-17