BAFFR activates PI3K/AKT signaling in human naive but not in switched memory B cells through direct interactions with B cell antigen receptors

Cell Rep. 2022 Jun 28;39(13):111019. doi: 10.1016/j.celrep.2022.111019.

Abstract

Binding of BAFF to BAFFR activates in mature B cells PI3K/AKT signaling regulating protein synthesis, metabolic fitness, and survival. In humans, naive and memory B cells express the same levels of BAFFR, but only memory B cells seem to survive without BAFF. Here, we show that BAFF activates PI3K/AKT only in naive B cells and changes the expression of genes regulating migration, proliferation, growth, and survival. BAFF-induced PI3K/AKT activation requires direct interactions between BAFFR and the B cell antigen receptor (BCR) components CD79A and CD79B and is enhanced by the AKT coactivator TCL1A. Compared to memory B cells, naive B cells express more surface BCRs, which interact better with BAFFR than IgG or IgA, thus allowing stronger responses to BAFF. As ablation of BAFFR in naive and memory B cells causes cell death independent of BAFF-induced signaling, BAFFR seems to act also as an intrinsic factor for B cell survival.

Keywords: BAFF; BAFFR; BCR; CP: Immunology; PI3K signaling; human memory B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Cell Activating Factor / immunology
  • B-Cell Activating Factor / metabolism
  • B-Cell Activation Factor Receptor* / immunology
  • B-Cell Activation Factor Receptor* / metabolism
  • Humans
  • Memory B Cells* / immunology
  • Memory B Cells* / metabolism
  • Phosphatidylinositol 3-Kinases* / immunology
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Proto-Oncogene Proteins c-akt* / immunology
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Receptors, Antigen, B-Cell* / immunology
  • Receptors, Antigen, B-Cell* / metabolism

Substances

  • B-Cell Activating Factor
  • B-Cell Activation Factor Receptor
  • Receptors, Antigen, B-Cell
  • TNFRSF13C protein, human
  • Proto-Oncogene Proteins c-akt