Essential role for CAML in follicular B cell survival and homeostasis

J Immunol. 2012 Apr 1;188(7):3009-18. doi: 10.4049/jimmunol.1101641. Epub 2012 Feb 20.

Abstract

Calcium-modulating cyclophilin ligand (CAML) is a ubiquitously expressed protein that is important during thymopoiesis. However, whether it serves a function in mature lymphocytes is unknown. In this article, we show that CAML is essential for survival of peripheral follicular (Fo) B cells. Conditional deletion of CAML in CD19-Cre transgenic mice caused a significant reduction in Fo cell numbers and increased rates of homeostatic proliferation. CAML-deficient Fo cells showed increased cellular turnover and normal proliferative ability. Although CAML-deficient Fo cells responded to AgR stimulation and to B cell activating factor, they displayed decreased survival and increased apoptosis following stimulation with LPS and IL-4 in vitro. Failure to survive was not due to aberrant B cell development in the absence of CAML, because induced deletion of the gene in mature cells resulted in a similar phenotype. These data establish an essential and ongoing role for CAML in the long-term survival of mature B cells.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / deficiency
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / physiology*
  • Adoptive Transfer
  • Animals
  • Apoptosis / drug effects
  • B-Cell Activating Factor / pharmacology
  • B-Lymphocyte Subsets / immunology*
  • Cell Survival
  • Homeostasis
  • Interleukin-4 / pharmacology
  • Lipopolysaccharides / pharmacology
  • Lymph Nodes / immunology
  • Lymph Nodes / ultrastructure
  • Mice
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Receptors, Antigen, B-Cell / immunology
  • Specific Pathogen-Free Organisms
  • Spleen / cytology
  • Spleen / immunology

Substances

  • Adaptor Proteins, Signal Transducing
  • B-Cell Activating Factor
  • Caml protein, mouse
  • Lipopolysaccharides
  • Receptors, Antigen, B-Cell
  • Interleukin-4