Immunoglobulin Heavy Chain Sequences Research Articles

Lymphocyte membrane IgG and secreted IgG are structurally and allotypically distinct.

We have demonstrated that there are structurally distinct membrane and secreted IgG2a immunoglobulin molecules. The membrane heavy chain is both larger and more acidic than the secreted molecule. This difference is not a result of different N-glycosidic-linked oligosaccharide chains. The membrane heavy chain also is antigenically different from its secreted homologue. This is based on the fact that secreted IgG2a molecules express an allotypic determinant absent on membrane molecules. We discussed the genetic control and gene organization of membrane and secreted immunoglobulin heavy chain sequences and suggest mechanisms controlling the expression of the simian virus 40 genome as models for alternate gene expression of membrane and secreted heavy chain polypeptide chains from the same DNA sequence. The possible biological significance of the membrane immunoglobulin acting as a recognition site for regulatory T cells also is discussed. The difference between membrane and secreted immunoglobulin is proposed as a possible explanation for the manner in which T cells interact with IgG on memory B cells in the presence of a large excess of IgG present in body fluids.

The conformation of human immunoglobulin D

1. Introduction Human immunoglobulin D (IgD) is present in low concentrations in normal human serum, usually less than 1% of the total immunoglobulin population [l] . Little is known of the physiological role of this immunoglobulin class since IgD molecules appear to lack the structural requirements for many effector functions, such as skin sensitisation and complement activation [2]. There have also been few reports of antibody activity associated with IgD. However, recent work suggests that IgD may be particularly active as a lymphocyte membrane antigen receptor [3]. Chemically-derived data, such as the lack of convincing homology of the ‘hinge’ region with other human immunoglobulin heavy chain sequences [4], the comparatively low proline content [5] , the distinctive susceptibility to proteolysis and high carbohydrate content [6], all suggest a unique structure of IgD within the general immunoglobulin structural pattern of two heavy and two light poly- peptide chains. We have studied two isolated IgD myeloma proteins using circular dichroism (CD) and isoelectric focusing (IEF) in order to try to clarify any unusual structural features of the molecule that could be responsible for the distinctive physiological behaviour of this immuno- globulin class. Neither the IEF pattern nor the CD spectra of IgD have been reported previously. 2. Materials and methods Serum from tyo patients (A and B) suffering from multiple myeloma (IiD) were generous gifts from 310 Dr I. C. M. MacLennan and Dr 0. Cromwell, respectively. Following precipitation with 19.3% ammonium sulphate containing 4%