The immunoglobulin genes

There are 214 immunoglobulin genes in the ensembl database of which 14 are related to the constant regions, 145 to the variable regions, 18 to the joining regions and 37 to the diversity regions of the resulting immunoglobulins. 148 of these genes are predicted secreted and have therefore been included in the secretome.

Immunoglobulins, or antibodies, are B cell produced glycoproteins critical for the adaptive immune response to bacteria and viruses. They exist in two forms, the membrane-bound antibodies that is part of the B-cell receptor complex binding the antigens, and the soluble antibodies secreted by plasma cells resulting from proliferation of antigen-activated B-cells. Antibodies consist of 2 heavy chains (H) and 2 light chains (L) that form Y-shaped molecules with two defined domains, the lower complement and phagocyte binding crystallizable Fc-domain and the upper antigen binding Fab domain. The Fc domain is composed entirely of H chain whereas the Fab domain consists of both H and L chains that are folded into constant(C) and variable (V) regions. The variable regions of the Fab domain contain the complementarity determining regions(CDRs) which consists of three hypervariable loops and allows for recognition of an almost unlimited number of antigens, while the constant regions provide a structural framework (see figure).

Functions of immunoglobulins

There are five types of human antibodies classified based on sequence differences in the Fc domain of the heavy chains. Immunoglobulin M (IgM) and immunoglobulin D (IgD) are the first antibodies to be produced upon infection and they are expressed on the surface of non-activated B-cells and mainly found in blood and lymph fluid. When a B-cell is then antigen-activated it will upon encountering specific signaling molecules undergo class switching to start to produce immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin E (IgE). IgG is the most abundant antibody type, it is found in all body fluids and protects against bacterial and viral infections. IgA is crucial for the immune function of the mucous membranes and between three and five grams are secreted into the intestinal lumen each day. IgE is associated with allergic reactions and is found in lungs, skin and mucous membranes. Class switching affects only the constant region of the antibody and therefore the antigen specificity stays the same and daughter cells from a single activated B-cell can produce antibodies of different classes.