title: CD138 mediates selection of mature plasma cells by regulating their survival.
abstract: Antibody secreting cells (ASCs) are critical effector cells and long-lived sentinels for immune memory. ASCs are highly dependent on exogenous soluble factors such as interleukin-6 (IL-6) and APRIL, to prevent their cell death. We have found that the canonical surface marker of ASCs, CD138 (syndecan-1), which is upregulated during ASC maturation, is required in a cell-intrinsic manner to mount an effective long-term humoral immune response following immunization. Surface expression of CD138 increased heparan sulfate levels on ASCs, which are known to bind pro-survival cytokines, leading to increased survival in a cell-intrinsic manner in vivo. In IL-6 and APRIL-deficient hosts, ASCs underwent extensive apoptosis independently of CD138 expression. We propose a model in which CD138 expression on fully mature ASCs provides a selective survival advantage over less mature, newly minted ASCs, by enhancing pro-survival cytokine signaling.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY; and.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: McCarron
authors.affiliation: Division of Newborn Medicine and.|Division of Respiratory Diseases, Children's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Pyong Woo
authors.initials: PW
authors.lastname: Park
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY; and.
authors.forename: David R
authors.initials: DR
authors.lastname: Fooksman
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D017209:Apoptosis; D002454:Cell Differentiation; D002470:Cell Survival; D000939:Epitopes / Q000276:immunology; D018858:Germinal Center / Q000276:immunology; D006801:Humans; D056724:Immunity, Humoral; D015850:Interleukin-6 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D010950:Plasma Cells / Q000166:cytology* / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D053668:Syndecan-1 / Q000378:metabolism*; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000378:metabolism
chemical_list: D000939:Epitopes; D015850:Interleukin-6; D053668:Syndecan-1; C491959:Tnfsf13 protein, mouse; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13