title: Lower levels of surface B-cell-receptor expression in chronic lymphocytic leukemia are associated with glycosylation and folding defects of the mu and CD79a chains.
abstract: Low levels of B-cell-receptor (BCR) expression are the hallmark of tumoral B lymphocytes in B-cell chronic lymphocytic leukemia (B-CLL). These cells also respond inadequately to stimulation through the BCR. This receptor consists of a surface immunoglobulin associated with a CD79a/CD79b heterodimer. We previously showed that the intracellular synthesis of BCR components, from transcription onward, is normal. Here, we investigated the glycosylation status and cellular localization of mu, CD79a, and CD79b chains in 10 CLL patients differing in surface immunoglobulin M (IgM) expression. We reported a severe impairment of the glycosylation and folding of mu and CD79a. These defects were associated with the retention of both chains in the endoplasmic reticulum and lower levels of surface IgM expression. In contrast, no clear impairment of glycosylation and folding was observed for CD79b. No sequence defects were identified for BCR components and for the chaperone proteins involved in BCR folding processes. These data show, for the first time, that lower levels of BCR surface expression observed in CLL are accounted for by an impaired glycosylation and folding of the mu and CD79a chains.
authors.affiliation: Unité d'Immuno-Hématologie et d'Immunopathologie, Plate-forme de Microscopie Electronique, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France. vuillier@pasteur.fr
authors.forename: Françoise
authors.initials: F
authors.lastname: Vuillier
authors.forename: Gérard
authors.initials: G
authors.lastname: Dumas
authors.forename: Christian
authors.initials: C
authors.lastname: Magnac
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Prevost
authors.forename: Ana Inés
authors.initials: AI
authors.lastname: Lalanne
authors.forename: Pablo
authors.initials: P
authors.lastname: Oppezzo
authors.forename: Evie
authors.initials: E
authors.lastname: Melanitou
authors.forename: Guillaume
authors.initials: G
authors.lastname: Dighiero
authors.forename: Béatrice
authors.initials: B
authors.lastname: Payelle-Brogard
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism / Q000648:ultrastructure; D051925:CD79 Antigens; D019281:Dimerization; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006031:Glycosylation; D006056:Golgi Apparatus / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007075:Immunoglobulin M / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D018832:Molecular Chaperones / Q000378:metabolism; D017510:Protein Folding; D011940:Receptor Aggregation; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D051925:CD79 Antigens; C497881:CD79A protein, human; D007075:Immunoglobulin M; D018832:Molecular Chaperones; D011947:Receptors, Antigen, B-Cell