Rap1 Is Essential for B-Cell Locomotion, Germinal Center Formation and Normal B-1a Cell Population
In: Frontiers in Immunology, Jg. 12 (2021-06-01)
Online
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Zugriff:
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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Rap1 Is Essential for B-Cell Locomotion, Germinal Center Formation and Normal B-1a Cell Population
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Autor/in / Beteiligte Person: | Ishihara, Sayaka ; Fukuyama, Hidehiro ; Sugioka, Risa ; Nakajima, Akihiko ; Miwa, Ryota ; Kotani, Ai ; Sato, Ryota ; Sawai, Satoshi ; Katagiri, Koko ; Sato, Tsuyoshi ; Saito, Haruka |
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Zeitschrift: | Frontiers in Immunology, Jg. 12 (2021-06-01) |
Veröffentlichung: | Frontiers Media S.A., 2021 |
Medientyp: | unknown |
ISSN: | 1664-3224 (print) |
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