Immunogetics Information Sytstem
Isotypes Expressed
Immunoglobulins are expressed in 2 forms: secreted antibody that is produced by plasma cells, and membrane bound antibody that associates with Ig-?/Ig-? heterodimers to form the B-cell antigen receptor present on the surface of B cells. B cells express different isotypes of membrane immunoglobulin (“mIg”) at different developmental stages. The immature B cells expressed only mIgM. mIgD appears later in maturation and is the predominant isotype on mature resting B cells. A memory B cell can express a variety of isotypes including combinations of mIgM, mIgG, mIgA and mIgE. Even when different isotypes are expressed on a single cell, the antigenic specificity of all the membrane antibody molecules is the same, so that each antibody molecule binds to the same epitope.
Within a species, each normal individual will express all isotypes in their serum. Different species inherit different constant region genes and therefore express different isotypes. (thus when antibody from one species is injected into another species, the isotypic determinants will be recognized as foreign, inducing an antibody response to the isotype. Such anti isotype antibody is often used to determine the class or subclass of serum antibody produced during an immune response or to characterize the class of membrane bound antibody present on B cells.
Although all members of a species inherit the same set of isotype genes, multiple alleles exist for some of the genes. It is well established that the constant regions of immunoglobulins, including human immunoglobulins, exist in various allotypes (the amino acid sequence of said constant regions may differ to a certan extent between individuals of a population). These alleles encode subtle aa differences, called “allotypic determinants” that occur in some members of a species. Each of these allotypic determinants represents differences in 1-3 aa that are encoded by different alleles. Antibody to allotypic determinants can be produced by injecting antibodies from one member of a species into another who lacks the allotypic determinant. Allotypes of the constant regions of human immunoglobulins are very well studied and the sequence information is readily available to the artisan from various sources, including the Immuno Genetics Information System.
Polyclonal Response of Immune Response
Native immune response does not generate a single antibody in response to disease, but instead a complex polyclonal response, comprised of multiple antibodies binding multiple epitopes with the ability to medaite a variety of effector functions. Targeting multiple epitopes offers braod strain protection and, unlike a monotherapy, is less likely to provide selective pressue for escape mutants already present in the population. The oeverall serum response recognizing a single antigen apepars to be oligoclonal with a discrete number of clades resulting from an initial VDJ recombination event folowed by somatic hypermutation. In the circulating repertoire, multiple clade members –not just highest affinity or most highly mutation, persist, perhaps to provide the plasticity to respond to anigenic variants. (Maynard, Current Opinion in Chemical Engineering, 2013, 2, 405-415).