Metabolic Links between Plasma Cell Survival, Secretion, and Stress

Humoral immunity is generated and maintained by antigen-specific antibodies that counter infectious pathogens. Plasma cells are the major producers of antibodies during and after infections, and each plasma cell produces some thousands of antibody molecules per second. This magnitude of secretion requires enormous quantities of amino acids and glycosylation sugars to properly build and fold antibodies, biosynthetic substrates to fuel endoplasmic reticulum (ER) biogenesis, and additional carbon sources to generate energy. Many of these processes are likely to be linked, thereby affording possibilities to improve vaccine design and to develop new therapies for autoimmunity. We review here aspects of plasma cell biology with an emphasis on recent studies and the relationships between intermediary metabolism, antibody production, and lifespan. Plasma cells secrete enormous quantities of antibodies and play crucial roles in humoral immunity and autoimmunity. This secretory activity underlies very specific metabolic requirements in this cell type. As B cells differentiate into plasma cells, marked changes in nutrient uptake and intermediary metabolism promote antibody synthesis and expansion of the ER. Some of the same substrates used for antibody synthesis and ER biogenesis are also used to generate energy and prevent plasma cell apoptosis. Differences in nutrient uptake thus correlate with plasma cell lifespan and antibody secretion rates. Expansion of the secretory apparatus in plasma cells triggers compensatory stress responses. Potential links between intermediary metabolism, ER stress, and plasma cell lifespan are starting to emerge.