Abstract

 

Random V(D)J junctions ensure that the diversity of the primary immunoglobulin (Ig) repertoire is adapted to the huge heterogeneity of antigens. In two thirds of cases, imprecise recombination between variable (V), diversity (D) and joining (J) segments induces a frameshift in the open reading frame that leads to the appearance of premature termination codons (PTCs). Thus, many B lineage cells harbor biallelic V(D)J-rearrangements of Ig heavy or light chain genes, with a productively-recombined allele encoding the functional Ig chain and a nonproductive allele potentially encoding truncated Ig polypeptides. Since the pattern of Ig gene expression is mostly biallelic, transcription initiated from nonproductive Ig alleles generates considerable amounts of primary transcripts with out-of-frame V(D)J junctions. How RNA surveillance pathways cooperate to control the noise from nonproductive Ig genes will be discussed in this review, with regard to the benefits of nonsense-mediated mRNA decay (NMD) activation during B-cell development and to the detrimental effects of nonsense-associated altered splicing (NAS) in terminally differentiated plasma cells.