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Pten controls B-cell responsiveness and germinal center reaction by regulating the expression of IgD BCR.
- Source :
-
The EMBO journal [EMBO J] 2019 Jun 03; Vol. 38 (11). Date of Electronic Publication: 2019 Apr 23. - Publication Year :
- 2019
-
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.<br /> (© 2019 The Authors. Published under the terms of the CC BY 4.0 license.)
- Subjects :
- Animals
Cells, Cultured
Forkhead Box Protein O1 physiology
Gene Expression Regulation immunology
Germinal Center metabolism
Immunoglobulin D immunology
Immunoglobulin D metabolism
Mice
Mice, Transgenic
PTEN Phosphohydrolase genetics
Receptors, Antigen, B-Cell metabolism
Signal Transduction genetics
Signal Transduction immunology
B-Lymphocytes physiology
Germinal Center physiology
Immunoglobulin D genetics
PTEN Phosphohydrolase physiology
Receptors, Antigen, B-Cell genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2075
- Volume :
- 38
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- The EMBO journal
- Publication Type :
- Academic Journal
- Accession number :
- 31015337
- Full Text :
- https://doi.org/10.15252/embj.2018100249