title: N-linked glycosylation selectively regulates autonomous precursor BCR function.
abstract: Developing B cells express distinct classes of B cell antigen receptors (BCRs) that differ in their heavy chain (HC). Although only muHC is expressed in early stages, deltaHC-containing BCRs dominate on the surface of mature B cells. The reason for the tightly regulated expression of these receptors is poorly understood. Here we show that muHC was specifically required for precursor BCR (pre-BCR) function and that deltaHC was unable to form a functional pre-BCR. A conserved asparagine (N)-linked glycosylation site at position 46 (N46) in the first conserved domain of muHC was absolutely required for pre-BCR function, and swapping that domain with deltaHC resulted in a functional deltaHC-containing pre-BCR. When tested in the context of the BCR, muHC with a mutant N46 showed normal function, which indicated that N46-glycosylation is specifically required for pre-BCR function. Our results suggest an unexpected mode of pre-BCR function, in which binding of the surrogate light chain to N46 mediates autonomous crosslinking and, concomitantly, receptor formation.
authors.affiliation: Center for Biological Signalling Studies, Albert-Ludwigs Universität Freiburg, Freiburg, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Ubelhart
authors.forename: Martina P
authors.initials: MP
authors.lastname: Bach
authors.forename: Cathrin
authors.initials: C
authors.lastname: Eschbach
authors.forename: Thomas
authors.initials: T
authors.lastname: Wossning
authors.forename: Michael
authors.initials: M
authors.lastname: Reth
authors.forename: Hassan
authors.initials: H
authors.lastname: Jumaa
mesh_terms: D000818:Animals; D001216:Asparagine / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D006031:Glycosylation; D007143:Immunoglobulin Heavy Chains / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D054420:Pre-B Cell Receptors / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*
chemical_list: D007143:Immunoglobulin Heavy Chains; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell; D001216:Asparagine