The tetraspanin CD81 regulates the expression of CD19 during B cell development in a postendoplasmic reticulum compartment.
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.
Shoham
Tsipi
T
Department of Medicine, Division of Oncology, Stanford University Medical Center, CA 94305-5151, USA.
Rajapaksa
Ranjani
R
Boucheix
Claude
C
Rubinstein
Eric
E
Poe
Jonathan C
JC
Tedder
Thomas F
TF
Levy
Shoshana
S
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018941:Antigens, CD19 / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000737:chemistry / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000737:chemistry / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006596:Hexosaminidases; D006801:Humans; D008297:Male; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase; D008562:Membrane Glycoproteins / Q000502:physiology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020033:Protein Isoforms / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D060225:Tetraspanin 28; D060245:Tetraspanin 29
D015703:Antigens, CD; D018941:Antigens, CD19; C554798:CD81 protein, human; C554869:CD9 protein, human; C554799:Cd81 protein, mouse; C554870:Cd9 protein, mouse; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D060225:Tetraspanin 28; D060245:Tetraspanin 29; D006596:Hexosaminidases; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase