title: Metabolomics of B to plasma cell differentiation.
abstract: When small B lymphocytes bind antigen in the context of suitable signals, a profound geno-proteomic metamorphosis is activated that generates antibody-secreting cells. To study the metabolic changes associated with this differentiation program, we compared the exometabolome of differentiating murine B lymphoma cells and primary B cells by monodimensional proton nuclear magnetic resonance spectroscopy and mass spectrometry coupled to liquid chromatography. Principal component analysis, a multivariate statistical analysis, highlighted metabolic hallmarks of the sequential differentiation phases discriminating between the proliferation and antibody secreting phases and revealing novel metabolic pathways. During proliferation, lactate production increased together with consumption of essential amino acids; massive Ig secretion was paralleled by alanine and glutamate production, glutamine being used as carbon and energy sources. Notably, ethanol and 5'-methylthioadenosine were produced during the last phase of protein secretion and the proliferative burst, respectively. Our metabolomics results are in agreement with previous genoproteomics studies. Thus, metabolic profiling of extracellular medium is a useful tool to characterize the functional state of differentiating B cells and to identify novel underlying metabolic pathways.
authors: Division of Genetics and Cell Biology, DiBiT, San Raffaele Scientific Institute, Milano, Italy. garciamanteiga.josemanuel@hsr.it
authors: Jose Manuel
authors: JM
authors: Garcia-Manteiga
authors: Silvia
authors: S
authors: Mari
authors: Markus
authors: M
authors: Godejohann
authors: Manfred
authors: M
authors: Spraul
authors: Claudia
authors: C
authors: Napoli
authors: Simone
authors: S
authors: Cenci
authors: Giovanna
authors: G
authors: Musco
authors: Roberto
authors: R
authors: Sitia
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D016393:Lymphoma, B-Cell / Q000473:pathology; D013058:Mass Spectrometry; D055442:Metabolome / Q000502:physiology*; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D019906:Nuclear Magnetic Resonance, Biomolecular; D010950:Plasma Cells / Q000166:cytology* / Q000378:metabolism*; D025341:Principal Component Analysis; D023302:Protein Footprinting