TY - JOUR
T1 - Galactocerebrosides are required postnatally for stromal-dependent bone marrow lymphopoiesis
AU - Katayama, Yoshio
AU - Frenette, Paul S.
N1 - Funding Information:
We are greatly thankful to Dr. Brian Popko for allowing us to analyze CGT −/− mice, Dr. Masao Iwamori (Kinki University, Osaka, Japan) for helpful suggestions on HPTLC analyses, Linnea Weiss for her excellent technical assistance, and Drs. Julio Aguirre-Ghiso and Lili Ossowski for providing FN-depleted serum. We are indebted to Drs. Richard Hynes, Brian Popko, Jay Unkeless, and Lloyd Mayer for critically reviewing the manuscript. We also thank Drs. Koichi Honke, Kateri Moore, and Joaquin Teixidó for providing reagents. This work was supported by the National Institutes of Health grants DK 56638 and HL 69438. Confocal laser scanning microscopy was performed at the MSSM-Microscopy Shared Resource Facility, supported by NIH-NCI shared resources grant CA-095823, NSF Major Research Instrumentation grant DBI-9724504, and NIH shared instrumentation grant 1S10 RR0 9145.
PY - 2003/6/1
Y1 - 2003/6/1
N2 - 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 CD45negVCAM-1pos 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.
AB - 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 CD45negVCAM-1pos 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.
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U2 - 10.1016/S1074-7613(03)00150-X
DO - 10.1016/S1074-7613(03)00150-X
M3 - Article
C2 - 12818160
AN - SCOPUS:0038771245
VL - 18
SP - 789
EP - 800
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 6
ER -