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

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Version: author
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_13E73B5B8C0A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
BAFFR activates PI3K/AKT signaling in human naive but not in switched memory B cells through direct interactions with B cell antigen receptors.
Journal
Cell reports
Author(s)
Sevdali E., Block V., Lataretu M., Li H., Smulski C.R., Briem J.S., Heitz Y., Fischer B., Ramirez N.J., Grimbacher B., Jäck H.M., Voll R.E., Hölzer M., Schneider P., Eibel H.
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
28/06/2022
Peer-reviewed
Oui
Volume
39
Number
13
Pages
111019
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
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
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, BAFF, BAFFR, BCR, CP: Immunology, PI3K signaling, human memory B cells
Pubmed
Create date
13/07/2022 11:49
Last modification date
21/11/2022 8:28
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