The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
B Cell Receptor and CD40 Signaling Are Rewired for Synergistic Induction of the c-Myc Transcription Factor in Germinal Center B Cells
Open accessAbstract
Summary Positive selection of germinal center (GC) B cells is driven by B cell receptor (BCR) affinity and requires help from follicular T helper cells. The transcription factors c‐Myc and Foxo1 are critical for GC B cell selection and survival. However, how different affinity‐related signaling events control these transcription factors in a manner that links to selection is unknown. Here we showed that GC B cells reprogram CD40 and BCR signaling to transduce via NF‐&kgr;B and Foxo1, respectively, whereas naive B cells propagate both signals downstream of either receptor. Although either BCR or CD40 ligation induced c‐Myc in naive B cells, both signals were required to highly induce c‐Myc, a critical mediator of GC B cell survival and cell cycle reentry. Thus, GC B cells rewire their signaling to enhance selection stringency via a requirement for both antigen receptor‐ and T cell‐mediated signals to induce mediators of positive selection. Graphical Abstract Figure. No Caption available. HighlightsIn GC B cells, CD40 signals via NF‐&kgr;B but not PI3K, while BCR does not activate NF‐&kgr;BWeak BCR signals in GC B cells propagate to Akt‐dependent phosphorylation of Foxo1In GC B cells, both CD40 and BCR signals are required to synergistically induce c‐MycCombined CD40 and BCR signals induce p‐S6 in GC B cells, permitting cell cycle entry &NA; Luo et al. show that CD40 and BCR signaling in GC B cells is rewired to control very different pathways, and both signals are required for optimal induction of c‐Myc, suggesting a mechanism of signaling‐directed positive selection of GC B cells.
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Cites
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T follicular helper cell biology: a decade of discovery and diseases
Crotty, S. (2019) · Immunity · doi:10.1016/j.immuni.2019.04.011 · Cited by 1,591
B cell memory: building two walls of protection against pathogens
Akkaya, M., Kwak, K., & Pierce, S. K. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0244-2 · Cited by 626
Germinal center‐derived lymphomas: The darkest side of humoral immunity
Mlynarczyk, C., Fontán, L., & Melnick, A. (2019) · Immunological Reviews · doi:10.1111/imr.12755 · Cited by 179
Selection in the germinal center
Lau, A. W., & Brink, R. (2020) · Current Opinion in Immunology · doi:10.1016/j.coi.2019.11.001 · Cited by 43
Lee, M. S. J., Inoue, T., Ise, W., Matsuo-Dapaah, J., Wing, J. B., Temizoz, B., Kobiyama, K., Hayashi, T., Patil, A., Sakaguchi, S., et al. (2022) · Journal of Experimental Medicine · doi:10.1084/jem.20211336 · Cited by 21
Metadata
- Authors
- Luo, W., Weisel, F., & Shlomchik, M. J.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 48
- Issue
- 2
- Pages
- 313-326.e5
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2787240390
- Cited by
- 325
- References
- 58
- FWCI
- 12.21
- Type
- journal article
- Language
- en
- Open access
- bronze
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