| First Author | Ben-Shalom N | Year | 2023 |
| Journal | Brain Behav Immun | Volume | 113 |
| Pages | 66-82 | PubMed ID | 37369341 |
| Mgi Jnum | J:338331 | Mgi Id | MGI:7510977 |
| Doi | 10.1016/j.bbi.2023.06.020 | Citation | Ben-Shalom N, et al. (2023) beta2-adrenergic signaling promotes higher-affinity B cells and antibodies. Brain Behav Immun 113:66-82 |
| abstractText | Stress-induced beta2-adrenergic receptor (beta2AR) activation in B cells increases IgG secretion; however, the impact of this activation on antibody affinity and the underlying mechanisms remains unclear. In the current study, we demonstrate that stress in mice following ovalbumin (OVA) or SARS-CoV-2 RBD immunization significantly increases both serum and surface-expressed IgG binding to the immunogen, while concurrently reducing surface IgG expression and B cell clonal expansion. These effects were abolished by pharmacological beta2AR blocking or when the experiments were conducted in beta2AR -/- mice. In the second part of our study, we used single B cell sorting to characterize the monoclonal antibodies (mAbs) generated following beta2AR activation in cultured RBD-stimulated B cells from convalescent SARS-CoV-2 donors. Ex vivo beta2AR activation increased the affinities of the produced anti-RBD mAbs by 100-fold compared to mAbs produced by the same donor control cultures. Consistent with the mouse experiments, beta2AR activation reduced both surface IgG levels and the frequency of expanded clones. mRNA sequencing revealed a beta2AR-dependent upregulation of the PI3K pathway and B cell receptor (BCR) signaling through AKT phosphorylation, as well as an increased B cell motility. Overall, our study demonstrates that stress-mediated beta2AR activation drives changes in B cells associated with BCR activation and higher affinity antibodies. |
