Effect of somatic hypermutation on potential N-glycosylation sites in human immunoglobulin heavy chain variable regions.
Immunoglobulins are known to be variably glycosylated. Although most carbohydrate is likely to be associated with the constant region, the variable region may also be glycosylated. Variable region glycosylation is known to be associated with antigen binding; in one model, the presence of carbohydrate on the external surface of CDR2 was shown to increase the affinity by up to ten-fold. In this study we have studied the effect of somatic hypermutation on potential sites of N-glycosylation in IgV(H) genes used by mucosal plasma cells secreting IgM, IgA and IgG in adults and children. Mucosal plasma cells secreting IgM, IgA and IgG are all heavily mutated from childhood. We have observed a tendency to lose the germline encoded N-glycosylation sites in all populations studied (a range of 43-67% of genes showing loss of the site). The tendency to lose the site was associated with a higher frequency of somatic hypermutation. We have also analysed the tendency to create potential N-glycosylation sites, and observed that this was greater in IgA and IgG than IgM and was again associated with the high frequency of somatic hypermutation. We observed no evidence of selection for either loss or gain of potential N-glycosylation sites. The changes in potential glycosylation status associated with a high frequency of somatic hypermutation is likely to increase the diversity of mucosal immunoglobulins, but is not as likely to affect the peripheral immune system where the frequency of somatic hypermutation is generally lower.
Dunn-Walters
D
D
Department of Histopathology, GKT Medical School, St Thomas' Campus, Lambeth Palace Road, SE1 7EH, London, UK.
Boursier
L
L
Spencer
J
J
D001483:Base Sequence; D006031:Glycosylation; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007422:Intestines / Q000166:cytology / Q000276:immunology*; D008969:Molecular Sequence Data; D009154:Mutation; D010950:Plasma Cells / Q000276:immunology*; D011499:Protein Processing, Post-Translational / Q000235:genetics*
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region