N-linked glycosylation selectively regulates autonomous precursor BCR function

• Published in: Nature immunology Vol. 11; no. 8; pp. 759 - 765
• Main Authors: Jumaa, Hassan, Reth, Michael, Bach, Martina P, Eschbach, Cathrin, Übelhart, Rudolf, Wossning, Thomas
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.08.2010; Nature Publishing Group
• Subjects: 631/250/1619/40/1774; 631/337/458/1524; 631/45/881; Animals; Asparagine - immunology; B-Lymphocytes - cytology; B-Lymphocytes - immunology; Biomedical and Life Sciences; Biomedicine; Cell receptors; Glycosylation; Immunoglobulin Heavy Chains - immunology; Immunoglobulins; Immunology; Infectious Diseases; Mice; Mice, Knockout; Physiological aspects; Pre-B Cell Receptors - immunology; Receptors, Antigen, B-Cell - immunology; Germany
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni.1903

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.