| First Author | Neely HR | Year | 2015 |
| Journal | J Immunol | Volume | 194 |
| Issue | 6 | Pages | 2616-23 |
| PubMed ID | 25662995 | Mgi Jnum | J:320730 |
| Mgi Id | MGI:6870864 | Doi | 10.4049/jimmunol.1401905 |
| Citation | Neely HR, et al. (2015) CXCL13 responsiveness but not CXCR5 expression by late transitional B cells initiates splenic white pulp formation. J Immunol 194(6):2616-23 |
| abstractText | Secondary lymphoid organs (SLO) provide the structural framework for coconcentration of Ag and Ag-specific lymphocytes required for an efficient adaptive immune system. The spleen is the primordial SLO, and evolved concurrently with Ig/TCR:pMHC-based adaptive immunity. The earliest cellular/histological event in the ontogeny of the spleen's lymphoid architecture, the white pulp (WP), is the accumulation of B cells around splenic vasculature, an evolutionarily conserved feature since the spleen's emergence in early jawed vertebrates such as sharks. In mammals, B cells are indispensable for both formation and maintenance of SLO microarchitecture; their expression of lymphotoxin alpha1beta2 (LTalpha1beta2) is required for the LTalpha1beta2:CXCL13 positive feedback loop without which SLO cannot properly form. Despite the spleen's central role in the evolution of adaptive immunity, neither the initiating event nor the B cell subset necessary for WP formation has been identified. We therefore sought to identify both in mouse. We detected CXCL13 protein in late embryonic splenic vasculature, and its expression was TNF-alpha and RAG-2 independent. A substantial influx of CXCR5(+) transitional B cells into the spleen occurred 18 h before birth. However, these late embryonic B cells were unresponsive to CXCL13 (although responsive to CXCL12) and phenotypically indistinguishable from blood-derived B cells. Only after birth did B cells acquire CXCL13 responsiveness, accumulate around splenic vasculature, and establish the uniquely splenic B cell compartment, enriched for CXCL13-responsive late transitional cells. Thus, CXCL13 is the initiating component of the CXCL13:LTalpha1beta2 positive feedback loop required for WP ontogeny, and CXCL13-responsive late transitional B cells are the initiating subset. |
