Survival of Igα-Deficient Mature B Cells Requires BAFF-R Function

J Immunol. 2016 Mar 1;196(5):2348-60. doi: 10.4049/jimmunol.1501707. Epub 2016 Feb 3.

Abstract

Expression of a functional BCR is essential for the development of mature B cells and has been invoked in the control of their maintenance. To test this maintenance function in a new experimental setting, we used the tamoxifen-inducible mb1-CreER(T2) mouse strain to delete or truncate either the mb-1 gene encoding the BCR signaling subunit Igα or the VDJ segment of the IgH (H chain [HC]). In this system, Cre-mediated deletion of the mb-1 gene is accompanied by expression of a GFP reporter. We found that, although the Igα-deficient mature B cells survive for >20 d in vivo, the HC-deficient or Igα tail-truncated B cell population is short-lived, with the HC-deficient cells displaying signs of an unfolded protein response. We also show that Igα-deficient B cells still respond to the prosurvival factor BAFF in culture and require BAFF-R signaling for their in vivo maintenance. These results suggest that, under certain conditions, the loss of the BCR can be tolerated by mature B cells for some time, whereas HC-deficient B cells, potentially generated by aberrant somatic mutations in the germinal center, are rapidly eliminated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Cell Activation Factor Receptor / antagonists & inhibitors
  • B-Cell Activation Factor Receptor / chemistry
  • B-Cell Activation Factor Receptor / genetics*
  • B-Cell Activation Factor Receptor / metabolism
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism*
  • Cell Survival / genetics
  • Endoplasmic Reticulum Stress
  • Gene Expression
  • Humans
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Phenotype
  • Protein Interaction Domains and Motifs / genetics*
  • Sequence Deletion
  • Signal Transduction

Substances

  • B-Cell Activation Factor Receptor
  • Tnfrsf13c protein, mouse