CXCL13 responsiveness but not CXCR5 expression by late transitional B cells initiates splenic white pulp formation.
J Immunol
; 194(6): 2616-23, 2015 Mar 15.
Article
en En
| MEDLINE
| ID: mdl-25662995
ABSTRACT
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/TCRpMHC-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 α1ß2 (LTα1ß2) is required for the LTα1ß2CXCL13 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-α 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 CXCL13LTα1ß2 positive feedback loop required for WP ontogeny, and CXCL13-responsive late transitional B cells are the initiating subset.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Bazo
/
Linfocitos B
/
Quimiocina CXCL13
/
Receptores CXCR5
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Pregnancy
Idioma:
En
Revista:
J Immunol
Año:
2015
Tipo del documento:
Article