2025-08-18 国立長寿医療研究センター,豊橋創造大学
図1. 老化関連B細胞(ABCs)は二次リンパ組織のT細胞領域に引き寄せられ、活発に運動しながらT細胞に働きかける。
<関連情報>
- https://www.ncgg.go.jp/ri/report/20250810.html
- https://www.ncgg.go.jp/ri/report/documents/Press_release_20250818.pdf
Fascin1とPak1の発現増加が、年齢に関連するB細胞のアクチン細胞骨格の再編成と運動性を向上させる Increased Fascin1 and Pak1 Expressions Enhance Age-Associated B-Cell Actin Cytoskeleton Remodeling and Motility
Mitsuhiro Fujiwara, Ryohei Kondo, Yuma Sugiyama, Mitsuo Maruyama, Akihiko Nishikimi
Cell Biochemistry and Function Published: 11 June 2025
DOI:https://doi.org/10.1002/cbf.70090
ABSTRACT
Age-associated B cells (ABCs), an atypical B-cell subset, tend to accumulate with age in mice and humans. These cells exhibit distinct characteristics, such as the ability to secrete antibodies and inflammatory cytokines upon stimulation of Toll-like receptor 7 (TLR7) and TLR9. Additionally, ABCs have been found to be more efficient in presenting antigens to T cells than follicular (FO) B cells. These features contribute to the development of pathogenic phenotypes in aging individuals. In this study, we demonstrated that actin cytoskeleton remodeling was enhanced in CD11b+/CD11c+ ABCs compared to CD11b–/CD11c– B cells. ABCs exhibited higher motility across Transwell membranes and three-dimensional (3D) collagen gels, even without chemoattractants. Due to the remodeling of chemokine receptor expression, ABCs were attracted by CXCL12 and CCL21 rather than CXCL13. Among F-actin remodeling-related factors, expression levels of Fascin1 and Pak1 were increased in ABCs. Treatment with the Pak1 inhibitor, IPA3, significantly attenuated ABC migration in Transwell chambers and 3D collagen gels. In contrast, the Fascin1 inhibitor, migrastatin, only reduced ABC migration in the 3D collagen gel. The increased expression of Fascin1 and Pak1 enhances actin cytoskeleton remodeling in ABCs, facilitating their dispersion within secondary lymphoid tissues.
Summary
- Age-associated B cells (ABCs), an atypical subset of B cells, tend to accumulate along with aging progressively.
- They have been found to exhibit higher motility and incorporate and present antigens to CD4+ T cells more efficiently than follicular B cells.
- Our findings revealed an increase in the expression of Fascin1 and Pak1 and the formation of fibrous actin in ABCs.
- The migration of ABCs through Transwell membranes and collagen gels was observed to be suppressed by a Pak1 inhibitor, while a Fascin1 inhibitor and knockdown selectively inhibited collagen gel migration.
- These findings suggest that Pak1 and Fascin1 are the specific molecules that govern the motility of ABCs, which serve as potent antigen-presenting cells moving within the T-cell zone.
