Phospholipid biosynthesis program underlying membrane expansion during B-lymphocyte differentiation
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Stimulated B-lymphocytes differentiate into plasma cells committed to antibody production. Expansion of the endoplasmic reticulum and Golgi compartments is a prerequisite for high rate synthesis, assembly, and secretion of immunoglobulins. The bacterial cell wall component lipopolysaccharide (LPS) stimulates murine B-cells to proliferate and differentiate into antibody-secreting cells that morphologically resemble plasma cells. LPS activation of CH12 B-cells augmented phospholipid production and initiated a genetic program, including elevated expression of the genes for the synthesis, elongation, and desaturation of fatty acids that supply the phospholipid acyl moieties. Likewise, many of the genes in phospholipid biosynthesis were up-regulated, most notably those encoding Lipin1 and choline phosphotransferase. In contrast, CTP:phosphocholine cytidylyltransferase alpha (CCTalpha) protein, a key control point in phosphatidylcholine biosynthesis, increased because of stabilization of protein turnover rather than transcriptional activation. Furthermore, an elevation in cellular diacylglycerol and fatty acid correlated with enhanced allosteric activation of CCTalpha by the membrane lipids. This work defines a genetic and biochemical program for membrane phospholipid biogenesis that correlates with an increase in the phospholipid components of the endoplasmic reticulum and Golgi compartments in LPS-stimulated B-cells.
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Plasma cell differentiation requires mitochondrial citrate to be converted to acetyl-CoA and oxaloacetate in the cytoplasm.
“Recent studies have suggested that plasma cells produce increased levels of phospholipids when compared to naïve B cells, and plasma cell differentiation is dependent on mitochondrial citrate conversion to acetyl-CoA and oxaloacetate in the cytoplasm (Dufort et al., 2014; Fagone et al., 2007).”
From Mitochondria in the Regulation of Innate and Adaptive Immunity (2015) · cites this paper as Fagone et al., 2007
Plasma cells contain more phospholipids than naïve B cells.
“Recent studies have suggested that plasma cells produce increased levels of phospholipids when compared to naïve B cells, and plasma cell differentiation is dependent on mitochondrial citrate conversion to acetyl-CoA and oxaloacetate in the cytoplasm (Dufort et al., 2014; Fagone et al., 2007).”
From Mitochondria in the Regulation of Innate and Adaptive Immunity (2015) · cites this paper as Fagone et al., 2007
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- Authors
- Fagone, P., Sriburi, R., Ward-Chapman, C., Frank, M., Wang, J., Gunter, C., Brewer, J. W., & Jackowski, S.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Loyola University Medical Center (US)
- Corresponding author
- Jackowski, Suzanne
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2007-03
- Volume
- 282
- Issue
- 10
- Pages
- 7591-7605
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2027845396
- Cited by
- 93
- References
- 62
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 5 · 2023: 6 · 2022: 9 · 2021: 6 · 2020: 4 · 2019: 1 · 2018: 6 · 2017: 3 · 2016: 3 · 2015: 6 · 2014: 3 · 2013: 3 · 2012: 6
- FWCI
- 4.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- American Lebanese Syrian Associated Charities (CA 21765)
- National Institutes of Health (CA21765))
- National Cancer Institute (CA21765, P30CA021765)
- National Institute of General Medical Sciences (R01GM061970, R01GM045737, GM61970, GM45737)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- phospholipid synthesis, B cell differentiation, plasma cell differentiation, lipopolysaccharide stimulation, endoplasmic reticulum expansion, immunoglobulin secretion, fatty acid elongation, fatty acid desaturation, LPIN1, cholinephosphotransferase, allosteric activation, diacylglycerol, membrane lipid signaling
- MeSH terms
- Animals, B-Lymphocytes, Cell Differentiation, Cell Membrane, Cells, Cultured, Diacylglycerol Cholinephosphotransferase, Diglycerides, Enzyme Activation, Lipopolysaccharides, Mice, Inbred C57BL, Phosphatidylcholines, Interleukin-5, Choline-Phosphate Cytidylyltransferase, Mice
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