N-linked glycosylation selectively regulates autonomous precursor BCR function
11.07.2010
Ubelhart R, Bach MP, Eschbach C, Wossning T, Reth M, Jumaa H.
Nat Immunol. 2010;11(8):759-65.
Developing B cells express distinct classes of B cell antigen receptors (BCRs) that differ in their heavy chain (HC). Although only mHC is expressed in early stages, dHC-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 mHC was specifically required for precursor BCR (pre-BCR) function and that dHC 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 mHC was absolutely required for pre-BCR function, and swapping that domain with dHC resulted in a functional dHC-containing pre-BCR. When tested in the context of the BCR, mHC 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.
