Distribution and Association of Heavy and Light Chain Variable Region Subgroups among Human IgA Immunoglobulins

Abstract

A series of randomly selected human IgA myeloma proteins were examined for the presence of the V_HIII subgroup, as defined by the possession of an unblocked amino terminal amino acid and characteristic linked residues along the heavy chain. Blocked heavy chains were classified as V_HB proteins. The data showed that 20 of 30 such random alpha chains (67%) were classifiable as members of the V_HIII subgroup. Similarly, 75% of heavy chains isolated from pools of normal serum IgA contained a V_HIII variable region. The pattern stands in marked contrast to the situation in human IgG proteins where approximately 20% of heavy chains from both pools and myeloma proteins are V_HIII. There was thus a clear divergence of the pattern of variable region: constant region association between these two classes of immunoglobulin.

Some more limited data were obtainable for the light chains of the IgA myeloma proteins. Certain predilections for light chain subgroup:heavy chain subgroup (V_HIII or V_HB) associations were discernable, but more data are required for definite conclusions.

Overall, this study suggests that although the pool of available variable region sequences is indeed shared among human IgA and IgG proteins, the partitioning is not exactly equivalent between the two immunoglobulin classes. The pattern is particularly apparent at present for the V_HIII subgroup which comprises approximately 70% of human alpha chains and only about 20% of human gamma chains.