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 carboh ydrate is likely to be associated with the constant region, the variable re gion may also be glycosylated. Variable region glycosylation is known to be associated with antigen binding; in one model, the presence of carbohydrat e 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 hypermutat ion on potential sites of N-glycosylation in IgV(H) genes used by mucosal p lasma cells secreting IgM, IgA and IgG in adults and children. Mucosal plas ma cells secreting IgM, IgA and IgG are all heavily mutated from childhood. We have observed a tendency to lose the germline encoded N-glycosylation s ites 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 freq uency of somatic hypermutation. We have also analysed the tendency to creat e potential N-glycosylation sites, and observed that this was greater in Ig A and IgG than IgM and was again associated with the high frequency of soma tic hypermutation. We observed no evidence of selection for either loss or gain of potential N-glycosylation sites. The changes in potential glycosyla tion status associated with a high frequency of somatic hypermutation is li kely to increase the diversity of mucosal immunoglobulins, but is not as li kely to affect the peripheral immune system where the frequency of somatic hypermutation is generally lower. (C) 2000 Elsevier Science Ltd. All rights reserved.