Alvarez et al.
Jan 12, 2024
This perspective article reviews
Antibodies are critical for human health, providing long-lived and exquisitely specific immunity to pathogens. Plasma cells secrete tens of thousands of antibody molecules every second and sustain this output continuously for several decades. Plasmablasts and plasma cells [collectively, antibody-secreting cells (ASCs)] are generated following the activation and differentiation of B cells, which involves complete reprogramming of the transcriptional machinery and remodeling of the endoplasmic reticulum and Golgi apparatus. ASCs have co-opted the unfolded protein response (UPR), a stress response, to accommodate the exceptional rate of protein synthesis and secretion required. On page 205 of this issue, Giguère et al. (1) reveal that mRNA encoding antibody genes is enriched with codons recognized by modified transfer RNA (tRNA). This codon optimization is accompanied by an increase in tRNAs with complementary modifications, which serves to enhance antibody biosynthesis by ASCs. This has wider implications for therapeutic protein production, vaccine design, and beyond.