| First Author | Davidzohn N | Year | 2020 |
| Journal | J Exp Med | Volume | 217 |
| Issue | 3 | PubMed ID | 31873727 |
| Mgi Jnum | J:289391 | Mgi Id | MGI:6432630 |
| Doi | 10.1084/jem.20191043 | Citation | Davidzohn N, et al. (2020) Syk degradation restrains plasma cell formation and promotes zonal transitions in germinal centers. J Exp Med 217(3) |
| abstractText | Germinal centers (GCs) are sites at which B cells proliferate and mutate their antibody-encoding genes in the dark zone (DZ), followed by affinity-based selection in the light zone (LZ). B cell antigen receptor (BCR) signals induce Syk activation followed by rapid phosphatase-mediated desensitization; however, how degradation events regulate BCR functions in GCs is unclear. Here, we found that Syk degradation restrains plasma cell (PC) formation in GCs and promotes B cell LZ to DZ transition. Using a mouse model defective in Cbl-mediated Syk degradation, we demonstrate that this machinery attenuates BCR signaling intensity by mitigating the Kras/Erk and PI3K/Foxo1 pathways, and restricting the expression of PC transcription factors in GC B cells. Inhibition of Syk degradation perturbed gene expression, specifically in the LZ, and enhanced the generation of PCs without affecting B cell proliferation. These findings reveal how long-lasting attenuation of signal transduction by degradation events regulates cell fate within specialized microanatomical sites. |
