Trends in Immunology
ReviewSeries: ImmunometabolismMetabolic Links between Plasma Cell Survival, Secretion, and Stress
Section snippets
Plasma Cell Formation and Subset Heterogeneity
The quality, quantity, and duration of antibody production by plasma cells are the major determinants of immunological protection against many infections and for almost all clinically used vaccines [1]. Plasma cells represent a unique lineage within the immune system, single-mindedly producing enormous quantities of antibodies for as long as they live. Recent studies have begun to uncover the intrinsic diversity of plasma cells, and with this information mechanistic details have emerged that
Intermediary Metabolism in Plasma Cell Formation and Maintenance
Much of the research on B cell metabolism during development and activation before plasma cell formation has been recently reviewed [3]. Thus, in this article we will focus on some key findings specifically related to intermediary metabolism, the process by which nutrients are converted into ATP and other cellular biosynthetic products. Naïve resting B cells have scant cytoplasm and ER, appear to have relatively few energy or biosynthetic requirements, and as such are recalcitrant to genetic
Antibody Secretion and ER Stress Responses in Plasma Cells
Though there are few unequivocal answers, to begin to address this question some background is required regarding how plasma cells metabolically acquire their secretory capacity and mount ER stress responses. Plasma cells are estimated to secrete several thousand antibody molecules per second [58]. To place this observation into a physiological context, only 1 μl of passively transferred immune serum is sufficient to protect an immunodeficient mouse from an otherwise lethal West Nile virus
Concluding Remarks
Despite the uncertainties listed above, some compelling evidence links specific ER stress, nutrient uptake, and antibody secretion pathways. Prdm1 not only promotes amino acid uptake in plasma cells but also promotes the expression of Xbp1 6, 7. Xbp1s then directs the diversion of glucose into the hexosamine pathway by enhancing the expression of rate-limiting enzymes [80], which may in turn promote antibody secretion 31, 56. Finally, the uptake of amino acids and glucose is linked to plasma
Acknowledgments
The authors are supported by National Institutes of Health (NIH) grant R01AI099108, the New York Stem Cell Foundation (NYSCF-R-I14), and a Research Scholar grant from the American Cancer Society (125091-RSG-13-252-01-LIB). D.B. is a New York Stem Cell Foundation Robertson Investigator.
Glossary
- Aerobic glycolysis
- metabolic pathway that converts glucose into pyruvate and then into lactate despite the presence of oxygen. Normally, when oxygen is present, pyruvate is carried into the mitochondria for oxidative phosphorylation, a highly efficient method for generating ATP. When pyruvate is instead converted into lactate in oxygen-replete conditions, this process is often referred to as Warburg metabolism, named after its discoverer Otto Warburg. Aerobic glycolysis is preferentially
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