Roughly half of mature B cells have biallelic rearrangements of immunoglobulin-encoding loci in which one allele encodes a nonfunctional protein due to frameshift mutations. Aberrantly rearranged alleles encoding the immunoglobulin-κ light chain can nevertheless generate truncated proteins via alternative RNA splicing. In The Journal of Experimental Medicine, Srour et al. reveal a previously unknown checkpoint in plasma cells that eliminates biallelically rearranged cells expressing truncated κ-chains. Premature termination codons within the variable (Vκ) exon can promote exon skipping, with transcripts retaining only the leader and constant regions. While mature and germinal center B cells tolerate expression of the κ-chains lacking V domains that arise from skipping of the Vκ exon, plasma cells show heightened endoplasmic reticulum stress when such truncated proteins are expressed and undergo rapid apoptosis, despite their expression of a second, functional allele. This checkpoint probably operates to eliminate those plasma cells bearing frameshift mutations as a result of somatic hypermutation.

J. Exp. Med. 213, 109–122 (2016)