Rap1 Is Essential for B-Cell Locomotion, Germinal Center Formation and Normal B-1a Cell Population.
Rap1 Is Essential for B-Cell Locomotion, Germinal Center Formation and Normal B-1a Cell Population.
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DOI：
10.3389/fimmu.2021.624419
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发表时间：
2021
影响因子：
7.3
通讯作者：
Katagiri K
中科院分区：
文献类型：
--
作者：
Ishihara S;Sato T;Sugioka R;Miwa R;Saito H;Sato R;Fukuyama H;Nakajima A;Sawai S;Kotani A;Katagiri K
Rap1 的整合素调节对于淋巴细胞再循环是必不可少的。在 B 细胞特异性 Rap1a/b 双敲除 (DKO) 小鼠中，淋巴结中 B 细胞数量减少至对照小鼠的约 4%，并且 B 细胞存在于脾脏和血液中。在用 NP-CGG 免疫后，DKO 小鼠表现出脾脏中 GC 形成有缺陷，并且 NP 特异性抗体产生减少。在体外，Rap1 缺陷会损害活化 B 细胞沿着趋化剂梯度的运动，而趋化剂对于它们在毛囊中的定位至关重要。此外，成年DKO小鼠的腹腔、脾脏和血液中几乎完全不存在B-1a细胞，并且新生儿和胎儿肝脏中B细胞祖细胞/前体（B-p）的数量减少。然而，DKO B-ps 在 IL-7 存在的情况下正常增殖并分化为 IgM+ 细胞。 Rap1 缺陷严重损害了 B-ps 在 VCAM-1 上的 CXCL12 依赖性迁移。胎儿肝脏的免疫染色研究揭示了 DKO B-ps 和产生 IL-7 的基质细胞共定位的缺陷。这项研究提出，Rap1 缺陷对体液反应和 B-1a 细胞生成的深远影响可能是由于或部分由趋化剂依赖性定位和与基质细胞接触的损伤所致。
Integrin regulation by Rap1 is indispensable for lymphocyte recirculation. In mice having B-cell-specific Rap1a/b double knockouts (DKO), the number of B cells in lymph nodes decreased to approximately 4% of that of control mice, and B cells were present in the spleen and blood. Upon the immunization with NP-CGG, DKO mice demonstrated the defective GC formation in the spleen, and the reduced NP-specific antibody production. In vitro, Rap1 deficiency impaired the movement of activated B cells along the gradients of chemoattractants known to be critical for their localization in the follicles. Furthermore, B-1a cells were almost completely absent in the peritoneal cavity, spleen and blood of adult DKO mice, and the number of B-cell progenitor/precursor (B-p) were reduced in neonatal and fetal livers. However, DKO B-ps normally proliferated, and differentiated into IgM+ cells in the presence of IL-7. CXCL12-dependent migration of B-ps on the VCAM-1 was severely impaired by Rap1 deficiency. Immunostaining study of fetal livers revealed defects in the co-localization of DKO B-ps and IL-7-producing stromal cells. This study proposes that the profound effects of Rap1-deficiency on humoral responses and B-1a cell generation may be due to or in part caused by impairments of the chemoattractant-dependent positioning and the contact with stromal cells.
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影响因子：
32.4
作者：
Bannard O;Horton RM;Allen CD;An J;Nagasawa T;Cyster JG
通讯作者：
Cyster JG
DOI：
10.1073/pnas.88.24.11550
发表时间：
1991-12-01
影响因子：
11.1
作者：
HARDY, RR;HAYAKAWA, K
通讯作者：
HAYAKAWA, K
影响因子：
5.3
作者：
Duchniewicz, M;Zemojtel, T;Zwartkiruis, FJT
通讯作者：
Zwartkiruis, FJT
影响因子：
20.3
作者：
Chen, Yuhong;Yu, Mei;Wang, Demin
通讯作者：
Wang, Demin
影响因子：
15.3
作者：
Hayakawa, K;Hardy, R R;Herzenberg, L A;Herzenberg, L A
通讯作者：
Herzenberg, L A