| First Author | Ishihara S | Year | 2021 |
| Journal | Front Immunol | Volume | 12 |
| Pages | 624419 | PubMed ID | 34140948 |
| Mgi Jnum | J:315042 | Mgi Id | MGI:6729385 |
| Doi | 10.3389/fimmu.2021.624419 | Citation | Ishihara S, et al. (2021) Rap1 Is Essential for B-Cell Locomotion, Germinal Center Formation and Normal B-1a Cell Population. Front Immunol 12:624419 |
| abstractText | 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. |
