Pten controls B-cell responsiveness and germinal center reaction by regulating the expression of IgD BCR

Journal article


Publication Details

Author(s): Setz CS, Khadour A, Renna V, Iype J, Gentner E, He X, Datta M, Young M, Nitschke L, Wienands J, Maity PC, Reth M, Jumaa H
Journal: EMBO Journal
Publication year: 2019
ISSN: 0261-4189
eISSN: 1460-2075


Abstract

In contrast to other B-cell antigen receptor (BCR) classes, the function of IgD BCR on mature B cells remains largely elusive as mature B cells co-express IgM, which is sufficient for development, survival, and activation of B cells. Here, we show that IgD expression is regulated by the forkhead box transcription factor FoxO1, thereby shifting the responsiveness of mature B cells towards recognition of multivalent antigen. FoxO1 is repressed by phosphoinositide 3-kinase (PI3K) signaling and requires the lipid phosphatase Pten for its activation. Consequently, Pten-deficient B cells expressing knock-ins for BCR heavy and light chain genes are unable to upregulate IgD. Furthermore, in the presence of autoantigen, Pten-deficient B cells cannot eliminate the autoreactive BCR specificity by secondary light chain gene recombination. Instead, Pten-deficient B cells downregulate BCR expression and become unresponsive to further BCR-mediated stimulation. Notably, we observed a delayed germinal center (GC) reaction by IgD-deficient B cells after immunization with trinitrophenyl-ovalbumin (TNP-Ova), a commonly used antigen for T-cell-dependent antibody responses. Together, our data suggest that the activation of IgD expression by Pten/FoxO1 results in mature B cells that are selectively responsive to multivalent antigen and are capable of initiating rapid GC reactions and T-cell-dependent antibody responses.


FAU Authors / FAU Editors

Nitschke, Lars Prof. Dr.
Professur für Genetik


External institutions with authors

Albert-Ludwigs-Universität Freiburg
Georg-August-Universität Göttingen
Universitätsklinikum Ulm


How to cite

APA:
Setz, C.S., Khadour, A., Renna, V., Iype, J., Gentner, E., He, X.,... Jumaa, H. (2019). Pten controls B-cell responsiveness and germinal center reaction by regulating the expression of IgD BCR. EMBO Journal. https://dx.doi.org/10.15252/embj.2018100249

MLA:
Setz, Corinna S., et al. "Pten controls B-cell responsiveness and germinal center reaction by regulating the expression of IgD BCR." EMBO Journal (2019).

BibTeX: 

Last updated on 2019-28-05 at 15:38