The tetraspanin CD81 regulates the expression of CD19 during B cell development in a postendoplasmic reticulum compartment

J Immunol. 2003 Oct 15;171(8):4062-72. doi: 10.4049/jimmunol.171.8.4062.

Abstract

CD81 is a widely expressed tetraspanin that associates in B cells with CD19 in the CD19-CD21-CD81 signaling complex. CD81 is necessary for normal CD19 expression; cd81(-/-) B cells express lower levels of CD19, especially cd81(-/-) small pre-BII cells, which are almost devoid of surface CD19. The dependence of CD19 expression on CD81 is specific to this particular tetraspanin since cd9(-/-) B cells express normal levels of CD19. Furthermore, expression of human CD81 in mouse cd81(-/-) B cells restored surface CD19 to normal levels. Quantitative analysis of CD19 mRNA demonstrated normal levels, even in cd81(-/-) pre-BII cells. Analysis of CD19 at the protein level identified two CD19 glycoforms in both wild-type and cd81(-/-) B cells. The higher M(r) glycoform is significantly reduced in cd81(-/-) B cells and is endoglycosidase H (endo-H) resistant. In contrast, the low M(r) glycoform is comparably expressed in cd81(-/-) and in wild-type B cells and is endo-H sensitive. Because endo-H sensitivity is tightly correlated with endoplasmic reticulum localization, we suggest that the dependency of CD19 expression on CD81 occurs in a postendoplasmic reticulum compartment where CD81 is necessary for normal trafficking or for surface membrane stability of CD19.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / biosynthesis
  • Antigens, CD / genetics
  • Antigens, CD / physiology*
  • Antigens, CD19 / analysis
  • Antigens, CD19 / biosynthesis*
  • Antigens, CD19 / metabolism
  • B-Lymphocyte Subsets / chemistry
  • B-Lymphocyte Subsets / cytology*
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism
  • Bone Marrow Cells / chemistry
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Line
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Endoplasmic Reticulum / chemistry
  • Endoplasmic Reticulum / immunology*
  • Endoplasmic Reticulum / metabolism*
  • Female
  • Hematopoietic Stem Cells / chemistry
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / metabolism
  • Hexosaminidases
  • Humans
  • Male
  • Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase
  • Membrane Glycoproteins / physiology
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Isoforms / analysis
  • Protein Isoforms / biosynthesis
  • Protein Isoforms / metabolism
  • RNA, Messenger / biosynthesis
  • Tetraspanin 28
  • Tetraspanin 29

Substances

  • Antigens, CD
  • Antigens, CD19
  • CD81 protein, human
  • CD9 protein, human
  • Cd81 protein, mouse
  • Cd9 protein, mouse
  • Membrane Glycoproteins
  • Membrane Proteins
  • Protein Isoforms
  • RNA, Messenger
  • Tetraspanin 28
  • Tetraspanin 29
  • Hexosaminidases
  • Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase