Autocrine secretion of interferon gamma negatively regulates homing of immature B cells.
The mechanism by which immature B cells are sequestered from encountering foreign antigens present in lymph nodes or sites of inflammation, before their final maturation in the spleen, has not been elucidated. We show here that immature B cells fail to home to the lymph nodes. These cells can actively exclude themselves from antigen-enriched sites by downregulating their integrin-mediated adhesion to the extracellular matrix protein, fibronectin. This inhibition is mediated by interferon gamma secretion. Perturbation of interferon gamma activity in vivo leads to the homing of immature B cells to the lymph nodes. This is the first example of autocrine regulation of immune cell migration to sites of foreign antigen presentation.
Flaishon
L
L
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Hershkoviz
R
R
Lantner
F
F
Lider
O
O
Alon
R
R
Levo
Y
Y
Flavell
R A
RA
Shachar
I
I
D000818:Animals; D019898:Autocrine Communication; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D016023:Integrins / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism* / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D017077:Culture Media, Conditioned; D005353:Fibronectins; D016023:Integrins; D007378:Interleukins; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate