Binding of free immunoglobulin light chains to VpreB3 inhibits their maturation and secretion in chicken B cells.
The VpreB3 gene product was first characterized as an immunoglobulin (Ig) mu heavy chain-binding protein in mouse precursor B (pre-B) cells. Although its function is unknown, it has been proposed to participate in the assembly and transport of the pre-B cell receptor. We have identified a VpreB3 orthologous gene in chicken that is located close to the immunoglobulin light chain (LC) gene cluster and specifically expressed in the bursa of Fabricius. By overexpressing VpreB3 in the DT40 IgM(+) immature chicken B cell line, we have characterized VpreB3 as an endoplasmic reticulum-resident glycoprotein that binds preferentially to free IgLC. However, binding to IgHC is observed in IgLC-deficient DT40 cells. Interaction of VpreB3 with free IgLC is partly covalent and induces retention of free IgLC in the endoplasmic reticulum, preventing their secretion without affecting IgM surface expression. Our results demonstrate that this evolutionarily conserved molecule may play a role in the regulation of the maturation and secretion of free IgLC in B cells. We discuss possible implications in the regulation of the immune response.
Rosnet
Olivier
O
Centre d'Immunologie de Marseille-Luminy, Centre National de la Recherche Scientifique-Institut National de la Santé et de la Recherche Médicale-Université de la Méditeranée, Campus de Luminy, 13288 Marseille Cedex 09, France. rosnet@ciml.univ-mrs.fr
Blanco-Betancourt
Carla
C
Grivel
Karine
K
Richter
Kirsten
K
Schiff
Claudine
C
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D002645:Chickens; D018076:DNA, Complementary / Q000378:metabolism; D019281:Dimerization; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D004721:Endoplasmic Reticulum; D005434:Flow Cytometry; D006026:Glycoside Hydrolases / Q000494:pharmacology; D006056:Golgi Apparatus; D006801:Humans; D015151:Immunoblotting; D007147:Immunoglobulin Light Chains / Q000737:chemistry*; D007075:Immunoglobulin M / Q000737:chemistry; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D008957:Models, Genetic; D008969:Molecular Sequence Data; D005810:Multigene Family; D054420:Pre-B Cell Receptors; D011233:Precipitin Tests; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014018:Tissue Distribution
D018076:DNA, Complementary; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D054420:Pre-B Cell Receptors; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; C515476:pre-B lymphocyte protein 3, human; D006026:Glycoside Hydrolases