Tyrosine kinase c-Abl regulates the survival of plasma cells

Sci Rep. 2017 Jan 6:7:40133. doi: 10.1038/srep40133.

Abstract

Tyrosine kinase c-Abl plays an important role in early B cell development. Its deletion leads to reduced pro- and pre-B cell generation in mice. However, its function in B cell terminal differentiation remains unexplored. Here, we used c-Ablf/f Aicdacre/+ mice, in which c-Abl is ablated only in antigen-activated B cells, to study the role of c-Abl in germinal center (GC) B and antibody-secreting plasma cell formation. Upon challenge with a model antigen, we found normal GC and memory B but reduced plasma cells and antigen-specific antibody response in the mutant mice. In-vitro studies revealed that plasma cells lacking c-Abl could be generated but did not accumulate in culture, indicative of survival defect. They also exhibited impaired STAT3 phosphorylation. The plasma cell defects could be rectified by introduction of Bim-deficiency or delivery of colivelin, a STAT3 activator, into c-Ablf/f Aicdacre/+ mice. Hence, c-Abl signalling regulates the survival of plasma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Survival
  • Female
  • Germinal Center / immunology
  • Germinal Center / metabolism
  • Immunity, Humoral
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phosphorylation
  • Plasma Cells / metabolism*
  • Proto-Oncogene Proteins c-abl / immunology
  • Proto-Oncogene Proteins c-abl / metabolism*

Substances

  • Proto-Oncogene Proteins c-abl