Splicing variants of grass carp (Ctenopharyngodon idellus) IL-21: Functions in IgM+ B cell proliferation and IgM secretion

Dev Comp Immunol. 2020 Sep;110:103728. doi: 10.1016/j.dci.2020.103728. Epub 2020 May 6.

Abstract

In mammals, interleukin 21 (IL-21) is a type I four-helical bundle cytokine produced by activated T cells that has pleiotropic functions on immune cells. Although IL-21 has been discovered in fish, the splicing variants of this cytokine and their functions on B cells are unclear. In this study, based on the original transcript of grass carp IL-21 (named gcIL-21sv1 in this study), two alternative splicing variants, named gcIL-21sv2 and gcIL-21sv3, were cloned and characterized. The protein sequences of gcIL-21sv1 and gcIL-21sv2 consist of four α-helixes, and only the six amino acid residues at the C-terminal are different. Unlike gcIL-21sv1 and gcIL-21sv2, gcIL-21sv3 lacks the C-terminal region. The expression analysis showed that gcIL-21sv1, gcIL-21sv2, and gcIL-21sv3 were constitutively expressed in all the tested tissues, and their expression could be significantly up-regulated by LPS and Poly (I:C) in head kidney leukocytes (HKLs), with the fold change of gcIL-21sv1 being higher than that of gcIL-21sv2 and gcIL-21sv3. Recombinant gcIL-21sv1 and gcIL-21sv2, but not gcIL-21sv3, could induce the proliferation of IgM+ B cells and the secretion of IgM, with the activity of gcIL-21sv1 being stronger than that of gcIL-21sv2, indicating that the C-terminal region plays important roles in the function of gcIL-21. Taken together, this study found that, like IL-21 in human and mouse, IL-21 splicing variants also exist in fish, and the regulatory activities of these variants in humoral immunity are differ, suggesting that grass carp may balance the immune response mediated by IL-21 through alternative splicing.

Keywords: B cell; Grass carp; IL-21; IgM; Splicing variant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Animals
  • B-Lymphocytes / immunology*
  • Carps / immunology*
  • Cell Proliferation
  • Cloning, Molecular
  • Fish Proteins / genetics
  • Fish Proteins / metabolism*
  • Head Kidney / immunology*
  • Humans
  • Immunity, Humoral
  • Immunoglobulin M / metabolism*
  • Interleukins / genetics
  • Interleukins / metabolism*
  • Leukocytes / immunology*
  • Lipopolysaccharides / immunology
  • Lymphocyte Activation
  • Mice
  • Poly I-C / immunology

Substances

  • Fish Proteins
  • Immunoglobulin M
  • Interleukins
  • Lipopolysaccharides
  • interleukin-21
  • Poly I-C