Developing lymph nodes collect CD4+CD3- LTbeta+ cells that can differentiate to APC, NK cells, and follicular cells but not T or B cells.
For a brief period during fetal lymph node organogenesis in mice, lymph node postcapillary high endothelial venules surprisingly express the Peyer's patch addressin MAdCAM-1. This expression allows initial seeding of this incipient structure by two unusual lymphocyte populations selectively expressing the Peyer's patch homing receptor integrin alpha4beta7: CD4+CD3- oligolineage progenitors and TCR gammadelta+ T cells. We show here that CD4+CD3- cells are lineage-restricted progenitors that express surface lymphotoxin-beta (LTbeta) and the chemokine receptor BLR1 and that can become natural killer cells, dendritic antigen-presenting cells, and follicular cells of unknown outcome, but these cells do not become T or B lymphocytes. Since the necessity of lymphotoxin in lymphoid organ development has been shown, we propose that the novel subset of CD4+CD3-LTbeta+ fetal cells is instrumental in the development of lymphoid tissue architecture.
Mebius
R E
RE
Department of Cell Biology and Immunology, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands. r.mebius.cell@med.vu.nl
Rennert
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P
Weissman
I L
IL
D000818:Animals; D000831:Animals, Newborn; D000938:Antigen-Presenting Cells / Q000166:cytology*; D001402:B-Lymphocytes / Q000166:cytology; D017252:CD3 Complex / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D015815:Cell Adhesion Molecules; D003602:Cytotoxicity, Immunologic; D019084:Fluorescent Antibody Technique, Indirect; D019204:GTP-Binding Proteins / Q000235:genetics; D015870:Gene Expression; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007111:Immunity, Cellular; D007136:Immunoglobulins / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D019891:Leukopoiesis; D008198:Lymph Nodes / Q000166:cytology / Q000196:embryology*; D016131:Lymphocyte Subsets / Q000166:cytology*; D008233:Lymphotoxin-alpha / Q000378:metabolism*; D053308:Lymphotoxin-beta; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009088:Mucoproteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000235:genetics; D013154:Spleen / Q000196:embryology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology
D017252:CD3 Complex; C513179:CXCR5 protein, mouse; D015815:Cell Adhesion Molecules; D000949:Histocompatibility Antigens Class II; D007136:Immunoglobulins; D016023:Integrins; D007376:Interleukin-2; C505886:LTB protein, human; C505887:Ltb protein, mouse; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; C489082:Madcam1 protein, mouse; D008565:Membrane Proteins; D009088:Mucoproteins; D012333:RNA, Messenger; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; C071777:integrin alpha4beta7; D017493:Leukocyte Common Antigens; D019204:GTP-Binding Proteins