樹状細胞が組織内をパトロールする際、メッセンジャー分子によって一つにまとめられている。 A messenger molecule keeps dendritic cells together on their patrol through the tissue
2023-07-17 マックス・プランク研究所
◆研究チームは動物モデルで新しい概念を見つけ、樹状細胞が血管に沿って一列に並び、移動することで三次元細胞ネットワークを形成することを明らかにしました。樹状細胞の移動を制御する重要なメッセンジャー分子としてFLT3リガンドが特定されました。これらの発見はがん治療に重要であり、将来的には個別の治療法の開発につながる可能性があります。
◆現在のデータは動物モデルのリンパ節の解析に基づいており、次の目標は人間を含むすべての組織で同じネットワーク組織原則が適用されるかどうかを調査することです。
<関連情報>
- https://www.mpg.de/20626218/migrating-dendritic-cells?c=2249
- https://www.sciencedirect.com/science/article/abs/pii/S0889159123001642
β2アドレナリンシグナルはより親和性の高いB細胞と抗体を促進する β2-adrenergic signaling promotes higher-affinity B cells and antibodies
Noam Ben-Shalom, Elad Sandbank, Lilach Abramovitz, Hadas Hezroni, Talia Levine, Estherina Trachtenberg, Nadav Fogel, Michael Mor, Ron Yefet, Liat Stoler-Barak, David Hagin, Akiko Nakai, Masaki Noda, Kazuhiro Suzuki, Ziv Shulman, Shamgar Ben-Eliyahu, Natalia T. Freund
Brain, Behavior, and Immunity Available online: 25 June 2023
DOI:https://doi.org/10.1016/j.bbi.2023.06.020
Abstract
Stress-induced β2-adrenergic receptor (β2AR) 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 β2AR blocking or when the experiments were conducted in β2AR -/- mice. In the second part of our study, we used single B cell sorting to characterize the monoclonal antibodies (mAbs) generated following β2AR activation in cultured RBD-stimulated B cells from convalescent SARS-CoV-2 donors. Ex vivo β2AR 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, β2AR activation reduced both surface IgG levels and the frequency of expanded clones. mRNA sequencing revealed a β2AR-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 β2AR activation drives changes in B cells associated with BCR activation and higher affinity antibodies.
