Galactocerebrosides are required postnatally for stromal-dependent bone marrow lymphopoiesis.
Galactocerebrosides (GCs) represent a major class of glycolipids in the nervous system. Here, we show that mice lacking the key enzyme to generate GCs, UDP-galactose:ceramide galactosyltransferase (CGT(-/-)), exhibit severe postnatal atrophy of all lymphoid organs, owing to a maturational arrest before the pro-B/T cell stage. This lineage-specific defect originates from the bone marrow (BM) stroma since it is not transplantable to irradiated wild-type recipients. Remarkably, CGT(-/-) long-term B lymphoid BM cultures displayed severe deficits in the number of CD45(neg)VCAM-1(pos) stromal cells and fibronectin matrix assembly, and produced floating macrophages rather than B lymphocytes. The fibronectin network was also altered in the CGT-deficient BM parenchyma. These results point to an essential role for galactolipids in the formation of fibronectin-enriched lymphoid-specific stromal niches in the BM.
Katayama
Yoshio
Y
Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Frenette
Paul S
PS
D000818:Animals; D001853:Bone Marrow / Q000502:physiology*; D001854:Bone Marrow Cells; D002678:Chimera / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism; D005699:Galactosylceramides / Q000502:physiology*; D005700:Galactosyltransferases / Q000235:genetics / Q000378:metabolism; D051147:Ganglioside Galactosyltransferase; D006412:Hematopoietic Stem Cells / Q000502:physiology; D008214:Lymphocytes / Q000502:physiology*; D038041:Lymphopoiesis / Q000502:physiology*; D051379:Mice
D005353:Fibronectins; D005699:Galactosylceramides; D005700:Galactosyltransferases; C511214:Ugt8a protein, mouse; D051147:Ganglioside Galactosyltransferase