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

Sevdali E, Block V, Lataretu M, Li H, Smulski CR, Briem JS, Heitz Y, Fischer B, Ramirez NJ, Grimbacher B, Jäck HM, Voll RE, Hölzer M, Schneider P, Eibel H (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Cell Reports Elsevier (Cell Press)

Book Volume: 39

Pages Range: 111019-

Journal Issue: 13

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.

Authors with CRIS profile

Hans-Martin Jäck Professur für Immunologie

Involved external institutions

Universitätsklinikum Freiburg DE Germany (DE) Université de Lausanne (UNIL) CH Switzerland (CH) Albert-Ludwigs-Universität Freiburg DE Germany (DE) Bariloche Atomic Centre / Centro Atómico Bariloche AR Argentina (AR) Friedrich-Schiller-Universität Jena DE Germany (DE) Robert Koch-Institut (RKI) DE Germany (DE)

How to cite

APA:

Sevdali, E., Block, V., Lataretu, M., Li, H., Smulski, C.R., Briem, J.S.,... Eibel, H. (2022). BAFFR activates PI3K/AKT signaling in human naive but not in switched memory B cells through direct interactions with B cell antigen receptors. Cell Reports, 39(13), 111019-. https://doi.org/10.1016/j.celrep.2022.111019

MLA:

Sevdali, Eirini, et al. "BAFFR activates PI3K/AKT signaling in human naive but not in switched memory B cells through direct interactions with B cell antigen receptors." Cell Reports 39.13 (2022): 111019-.

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