Regulated expression of peripheral node addressin-positive high endothelial venules controls seeding of B lymphocytes into developing neonatal rabbit appendix.
Young rabbit appendix is a homologue of chicken bursa of Fabricius; both are crucial sites for preimmune B-cell repertoire diversification. Here, we report that appendix regulates precursor lymphocyte recruitment for further development by modulating the sites of extravasation. The total area of peripheral node addressin-positive (PNAd(+)) high endothelial venules (HEVs) increased from 1 day to 1 week after birth, remained constant up to 2 weeks and declined to a low and persistent amount by 3 weeks. In normal 1-week and manipulated 5-week appendix where growth of follicles was retarded, PNAd(+) HEVs were present in the basolateral sides of B-cell follicles whereas, in normal 5-wk-appendix these were restricted to T-cell areas. The PNAd was expressed on the lumenal surface of HEVs. The proportions of CD62L(+) B cells in appendix declined from approximately 40% at 3 days to 2-3% at 4 weeks. In lymphocyte transfer experiments, CD62L(+) B cells were preferentially recruited compared with CD62L(-) B cells, anti-PNAd antibody blocked migration of B cells by approximately 50%, and 100 times more B cells were recruited in 1-week compared to 6-week appendix. Thus, a unique spatiotemporal expression pattern of PNAd(+) HEVs is associated with development of B-cell follicles. This regulates migration of blood-borne B-lymphocytes into developing appendix by interacting with CD62L.
Sinha
Rajesh K
RK
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11N311, 10 Center Drive-MSC 1892, Bethesda, MD 20892, USA.
Alexander
Cornelius
C
Mage
Rose G
RG
D000818:Animals; D000831:Animals, Newborn; D000954:Antigens, Surface / Q000276:immunology; D001065:Appendix / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D005434:Flow Cytometry; D007150:Immunohistochemistry; D019041:L-Selectin / Q000276:immunology; D042601:Lymphatic Vessels / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology; D011817:Rabbits / Q000276:immunology*
D000954:Antigens, Surface; C069886:L-selectin counter-receptors; D008565:Membrane Proteins; D019041:L-Selectin