N-linked glycosylation selectively regulates autonomous precursor BCR function

Nat Immunol. 2010 Aug;11(8):759-65. doi: 10.1038/ni.1903. Epub 2010 Jul 11.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asparagine / immunology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Glycosylation
  • Immunoglobulin Heavy Chains / immunology*
  • Mice
  • Mice, Knockout
  • Pre-B Cell Receptors / immunology*
  • Receptors, Antigen, B-Cell / immunology*

Substances

  • Immunoglobulin Heavy Chains
  • Pre-B Cell Receptors
  • Receptors, Antigen, B-Cell
  • Asparagine