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

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.

Automated summary

The binding of BAFF to BAFFR activates PI3K/AKT signaling in mature B cells, regulating protein synthesis, metabolic fitness, and survival. While both naive and memory B cells express the same levels of BAFFR, only memory B cells can survive without BAFF. BAFF activates PI3K/AKT specifically in naive B cells and affects the expression of genes involved in migration, proliferation, growth, and survival. The activation of PI3K/AKT by BAFF requires direct interactions between BAFFR and BCR components CD79A and CD79B, and is enhanced by the AKT coactivator TCL1A. Compared to memory B cells, naive B cells have more surface BCRs that interact better with BAFFR, allowing stronger responses to BAFF. BAFFR also acts as an intrinsic factor for B cell survival as its ablation in both naive and memory B cells leads to cell death independent of BAFF-induced signaling.