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 mu HC is expressed in early stages, delta HC-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 mu HC was specifically required for precursor BCR (pre-BCR) function and that delta HC 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 mu HC was absolutely required for pre-BCR function, and swapping that domain with delta HC resulted in a functional delta HC-containing pre-BCR. When tested in the context of the BCR, mu HC 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.