Galactocerebrosides Are Required Postnatally for Stromal-Dependent Bone Marrow Lymphopoiesis

Immunity. 2003 Jun;18(6):789-800. doi: 10.1016/s1074-7613(03)00150-x.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Marrow / physiology*
  • Bone Marrow Cells
  • Chimera / physiology
  • Fibronectins / metabolism
  • Galactosylceramides / physiology*
  • Galactosyltransferases / genetics
  • Galactosyltransferases / metabolism
  • Ganglioside Galactosyltransferase
  • Hematopoietic Stem Cells / physiology
  • Lymphocytes / physiology*
  • Lymphopoiesis / physiology*
  • Mice

Substances

  • Fibronectins
  • Galactosylceramides
  • Galactosyltransferases
  • Ugt8a protein, mouse
  • Ganglioside Galactosyltransferase