title: Phospholipid biosynthesis program underlying membrane expansion during B-lymphocyte differentiation.
abstract: 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.
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, USA.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fagone
authors.forename: Rungtawan
authors.initials: R
authors.lastname: Sriburi
authors.forename: Cheryl
authors.initials: C
authors.lastname: Ward-Chapman
authors.forename: Matthew
authors.initials: M
authors.lastname: Frank
authors.forename: Jina
authors.initials: J
authors.lastname: Wang
authors.forename: Christopher
authors.initials: C
authors.lastname: Gunter
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Brewer
authors.forename: Suzanne
authors.initials: S
authors.lastname: Jackowski
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D019916:Choline-Phosphate Cytidylyltransferase / Q000378:metabolism; D002798:Diacylglycerol Cholinephosphotransferase / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D004789:Enzyme Activation; D015848:Interleukin-5 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D010713:Phosphatidylcholines / Q000096:biosynthesis*
chemical_list: D004075:Diglycerides; D015848:Interleukin-5; D008070:Lipopolysaccharides; D010713:Phosphatidylcholines; D019916:Choline-Phosphate Cytidylyltransferase; D002798:Diacylglycerol Cholinephosphotransferase