Antibody production relies on the tRNA inosine wobble modification to meet biased codon demand

Antibodies are produced at high rates to provide immunoprotection, which puts pressure on the B cell translational machinery. Here, we identified a pattern of codon usage conserved across antibody genes. One feature thereof is the hyperutilization of codons which lack genome-encoded Watson–Crick tRNAs, instead relying on the post-transcriptional tRNA modification inosine (I34), which expands the decoding capacity of specific tRNAs through wobbling. Antibody-secreting cells had increased I34 levels and were more reliant on I34 for protein production than naive B cells. Furthermore, antibody I34-dependent codon usage may influence B cell passage through regulatory checkpoints. Our work elucidates the interface between the tRNA pool and protein production in the immune system and has implications for the design and selection of antibodies for vaccines and therapeutics.

Methods
tRNA sequences from J558, MPC11, WEHI231, and Bcl clone 5b1b. See Methods and Materials, sections on "RNA extraction" and "tRNA sequencing". The raw, unpaired sequence FASTQ files are provided.