CD138 mediates selection of mature plasma cells by regulating their survival

Blood. 2017 May 18;129(20):2749-2759. doi: 10.1182/blood-2017-01-761643. Epub 2017 Apr 5.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation / immunology
  • Apoptosis
  • Cell Differentiation*
  • Cell Survival
  • Epitopes / immunology
  • Germinal Center / immunology
  • Humans
  • Immunity, Humoral
  • Interleukin-6 / metabolism
  • Mice, Inbred C57BL
  • Plasma Cells / cytology*
  • Plasma Cells / metabolism*
  • Signal Transduction / immunology
  • Syndecan-1 / metabolism*
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / metabolism

Substances

  • Epitopes
  • Interleukin-6
  • Syndecan-1
  • Tnfsf13 protein, mouse
  • Tumor Necrosis Factor Ligand Superfamily Member 13