Plasma cells: You are what you eat

Abstract

Summary Plasma cells are terminally differentiated B lymphocytes that constitutively secrete antibodies. These antibodies can provide protection against pathogens, and their quantity and quality are the best clinical correlates of vaccine efficacy. As such, plasma cell lifespan is the primary determinant of the duration of humoral immunity. Yet dysregulation of plasma cell function can cause autoimmunity or multiple myeloma. The longevity of plasma cells is primarily dictated by nutrient uptake and non‐transcriptionally regulated metabolic pathways. We have previously shown a positive effect of glucose uptake and catabolism on plasma cell longevity and function. In this review, we discuss these findings with an emphasis on nutrient uptake and its effects on respiratory capacity, lifespan, endoplasmic reticulum stress, and antibody secretion in plasma cells. We further discuss how some of these pathways may be dysregulated in multiple myeloma, potentially providing new therapeutic targets. Finally, we speculate on the connection between plasma cell intrinsic metabolism and systemic changes in nutrient availability and metabolic diseases.

Quantitative evaluation of protective antibody response induced by hepatitis E vaccine in humans

“…The vaccine-specific antibody lineages declined to the baseline within a month after the second and the third dose, which suggests the formation of B-cell memory following the plasmablast responses to the vaccine boosts 24 . However, the anti-HEV IgG in serum showed a continuous increase, which could be explained by the accumulation of secreted antibodies with higher affinity, or by the expanded PC population in the secondary lymph nodes, spleen, and bone marrow (a major site for long-lived PCs) 38 .…”

CD20 as a gatekeeper of the resting stage of human B cells

“…For surfaceome screening 50 million cells per replicate of Ramos WT, CD20KO-N and CD20KO-L were harvested and washed with ice-cold PBS. CSC was performed as previously described 23 . Deamidated peptides derived from N-glycosylated cell surface-residing receptors were analysed on a Q Exactive plus HF mass spectrometer (QE-HF MS) Thermo Scientific) coupled to an EASY-nLC 1200 instrument.…”

“…Plasma cells are large cells with an extended endoplasmic reticulum (ER) and a high rate of antibody production. Plasma cells thus have a higher demand for energy and biosynthetic precursor molecules than B lymphocytes 23,24 . To characterize the metabolic program of WT and KO-L Ramos cells we performed metabolic flux experiments and untargeted metabolomics analyses.…”

Metabolic Reprogramming Induces Immune Cell Dysfunction in the Tumor Microenvironment of Multiple Myeloma

“…This phenomenon is known as the Warburg effect ( 6 ), which is a hallmark of cancers, and is utilized in the 18F-fluorodeoxyglucose PET (18F- FDG–PET) as a sensitive diagnostic and prognostic tool in clinic ( 7 , 8 ). MM is also reported to be dependent on glycolysis due to an elevated glycolytic gene profile, as well as its susceptibility to glycolysis inhibitors, such as inhibitors of glucose transporter (GLUT) and key glycolytic enzyme ( 9 ). The GLUT family comprises of 14 GLUT subtypes ( 10 ), among which GLUT1 overexpression is associated with poor clinical outcomes in various cancers.…”