N-linked glycosylation selectively regulates autonomous precursor BCR function
Functional μ-immunoglobulin heavy chains pair with VpreB and λ5 to form precursor B cell antigen receptors. Jumaa and colleagues show that glycosylation at asparagine 46, a unique modification specific to the μ-heavy chain, is required for the function of such receptors. Developing B cells express d...
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Published in | Nature immunology Vol. 11; no. 8; pp. 759 - 765 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Nature Publishing Group US
01.08.2010
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | Functional μ-immunoglobulin heavy chains pair with VpreB and λ5 to form precursor B cell antigen receptors. Jumaa and colleagues show that glycosylation at asparagine 46, a unique modification specific to the μ-heavy chain, is required for the function of such receptors.
Developing B cells express distinct classes of B cell antigen receptors (BCRs) that differ in their heavy chain (HC). Although only μHC is expressed in early stages, δHC-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 μHC was specifically required for precursor BCR (pre-BCR) function and that δHC 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 μHC was absolutely required for pre-BCR function, and swapping that domain with δHC resulted in a functional δHC-containing pre-BCR. When tested in the context of the BCR, μHC 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 |
ISSN: | 1529-2908 1529-2916 |
DOI: | 10.1038/ni.1903 |