The Tetraspanin CD81 Regulates the Expression of CD19 During B Cell Development in a Postendoplasmic Reticulum Compartment

• Published in: The Journal of immunology (1950) 2003-10, Vol.171 (8), p.4062-4072
• Main Authors: Shoham, Tsipi, Rajapaksa, Ranjani, Boucheix, Claude, Rubinstein, Eric, Poe, Jonathan C, Tedder, Thomas F, Levy, Shoshana
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.171.8.4062

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.