Contribution of B-1a cells to systemic lupus erythematosus in the NZM2410 mouse model

Ann N Y Acad Sci. 2015 Dec;1362(1):215-23. doi: 10.1111/nyas.12607. Epub 2015 Feb 26.

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease of complex etiology in which B cells play a central role. An expanded number of B-1a cells have been consistently associated with murine lupus, and more recently with human SLE. We have identified Cdkn2c, a gene that controls cell cycle progression, as a key regulator of B-1a cell numbers and have associated Cdkn2c deficiency with autoimmune pathology, including the production of autoantibodies and the skewing of CD4(+) T cells toward inflammatory effector functions. We review the genetic studies that have led to these findings, as well as the possible mechanisms by which B-1a cell expansion and Cdkn2c deficiency are related to SLE pathogenesis.

Keywords: B-1a cell; NZM2410 mice; systemic lupus erythematosus.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • B-Lymphocyte Subsets / physiology*
  • Cyclin-Dependent Kinase Inhibitor p18 / deficiency*
  • Cyclin-Dependent Kinase Inhibitor p18 / genetics*
  • Disease Models, Animal*
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / metabolism*
  • Mice

Substances

  • Cdkn2c protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p18