N-linked glycosylation selectively regulates autonomous precursor BCR function.
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.
Ubelhart
Rudolf
R
Center for Biological Signalling Studies, Albert-Ludwigs Universität Freiburg, Freiburg, Germany.
Bach
Martina P
MP
Eschbach
Cathrin
C
Wossning
Thomas
T
Reth
Michael
M
Jumaa
Hassan
H
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*
D007143:Immunoglobulin Heavy Chains; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell; D001216:Asparagine