Membrane Lipid Biogenesis in B‐Lymphocytes

Abstract

Stimulated B‐lymphocytes differentiate into plasma cells committed to immunoglobulin production. The B‐cells proliferate and expand the endoplasmic reticulum to enhance immunoglobulin synthesis and secretion. Cellular membrane lipid components increase in response to stimulation using a genetic and biochemical program of events. Selected genes in fatty acid and phospholipid synthesis are up‐regulated, most notably the genes encoding Lipin1 and the choline phosphotransferase. The choline cytidylyltransferase (CCT) controls the rate of phosphatidylcholine production but its expression does not increase. Rather, the protein is stabilized and activated allosterically by association with intracellular membranes whose lipid composition changes. Two CCT isoforms are expressed in B‐cells. Knockout of the major CCTα isoform impairs proliferation, resulting in B cells that are unable to undergo immunoglobulin gene re‐arrangement and cannot switch from IgM to IgG production in response to immunization. IgM secretion is maintained in the knockouts, however, due to expression of the alternate isoform CCTβ2. These data suggest either different roles for the CCT isoforms or that a threshold of CCT protein is required to support both proliferation and secretion in B‐cells. Supported by NIH GM45737 (S.J.), GM61970 (J.W.B) and by ALSAC.