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

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 (2019)

Publication Type: Journal article

Publication year: 2019

Journal

EMBO Journal EMBO Press

Article Number: e100249

DOI: 10.15252/embj.2018100249

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.

Authors with CRIS profile

Lars Nitschke Professur für Genetik

Involved external institutions

Universitätsklinikum Ulm DE Germany (DE) Albert-Ludwigs-Universität Freiburg DE Germany (DE) Georg-August-Universität Göttingen DE Germany (DE)

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).

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