Sonic hedgehog is produced by follicular dendritic cells and protects germinal center B cells from apoptosis.
The Hedgehog (Hh) signaling pathway is involved in the development of many tissues during embryogenesis, but has also been described to function in adult self-renewing tissues. In the immune system, Sonic Hedgehog (Shh) regulates intrathymic T cell development and modulates the effector functions of peripheral CD4(+) T cells. In this study we investigate whether Shh signaling is involved in peripheral B cell differentiation in mice. Shh is produced by follicular dendritic cells, mainly in germinal centers (GCs), and GC B cells express both components of the Hh receptor, Patched and Smoothened. Blockade of the Hh signaling pathway reduces the survival, and consequently the proliferation and Ab secretion, of GC B cells. Furthermore, Shh rescues GC B cells from apoptosis induced by Fas ligation. Taken together, our data suggest that Shh is one of the survival signals provided by follicular dendritic cells to prevent apoptosis in GC B cells.
Sacedón
Rosa
R
Department of Cell Biology, Faculty of Medicine, Complutense University, Madrid, Spain.
Díez
Blanca
B
Nuñez
Vanesa
V
Hernández-López
Carmen
C
Gutierrez-Frías
Cruz
C
Cejalvo
Teresa
T
Outram
Susan V
SV
Crompton
Tessa
T
Zapata
Agustín G
AG
Vicente
Angeles
A
Varas
Alberto
A
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D020566:Dendritic Cells, Follicular / Q000378:metabolism*; D005260:Female; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D006131:Growth Inhibitors / Q000494:pharmacology; D053823:Hedgehog Proteins; D008198:Lymph Nodes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology*; D015854:Up-Regulation; D014704:Veratrum Alkaloids / Q000494:pharmacology
D019138:Antibodies, Blocking; D006131:Growth Inhibitors; D053823:Hedgehog Proteins; C465570:Shh protein, mouse; D015534:Trans-Activators; D014704:Veratrum Alkaloids; C000541:cyclopamine