Biology » The Immune System » Antibodies

Antibody Structure

An antibody, also known as an immunoglobulin (Ig), is a protein that is produced by plasma cells after stimulation by an antigen. Antibodies are the functional basis of humoral immunity. Antibodies occur in the blood, in gastric and mucus secretions, and in breast milk. Antibodies in these bodily fluids can bind pathogens and mark them for destruction by phagocytes before they can infect cells.

Antibody Structure

An antibody molecule is comprised of four polypeptides: two identical heavy chains (large peptide units) that are partially bound to each other in a “Y” formation, which are flanked by two identical light chains (small peptide units), as illustrated in the figure below. Bonds between the cysteine amino acids in the antibody molecule attach the polypeptides to each other. The areas where the antigen is recognized on the antibody are variable domains and the antibody base is composed of constant domains.

In germ-line B cells, the variable region of the light chain gene has 40 variable (V) and five joining (J) segments. An enzyme called DNA recombinase randomly excises most of these segments out of the gene, and splices one V segment to one J segment. During RNA processing, all but one V and J segment are spliced out. Recombination and splicing may result in over 106 possible VJ combinations. As a result, each differentiated B cell in the human body typically has a unique variable chain. The constant domain, which does not bind antibody, is the same for all antibodies.

Part A shows the arrangement of gene segments encoding antibody light chains in a germ-line B cell. The segment contains forty consecutive V regions, named V1 through V 40, five consecutive J regions named J1 through J5, and a constant region. J5 and the constant region are separated by an intron. DNA recombinase splices out the portion of DNA containing segments V3 through J1, resulting in a differentiated B cell. The gene is transcribed into pre-RNA. RNA processing splices out all but the V2, J2 and C regions. Translation results in a protein with a variable region formed from the V2 and J2 segments, and a constant region formed from the C region. The light chain joins the heavy chain to form a Y-shaped antibody.

(a) As a germ-line B cell matures, an enzyme called DNA recombinase randomly excises V and J segments from the light chain gene. Splicing at the mRNA level results in further gene rearrangement. As a result, (b) each antibody has a unique variable region capable of binding a different antigen.

Similar to TCRs and BCRs, antibody diversity is produced by the mutation and recombination of approximately 300 different gene segments encoding the light and heavy chain variable domains in precursor cells that are destined to become B cells. The variable domains from the heavy and light chains interact to form the binding site through which an antibody can bind a specific epitope on an antigen. The numbers of repeated constant domains in Ig classes are the same for all antibodies corresponding to a specific class. Antibodies are structurally similar to the extracellular component of the BCRs, and B cell maturation to plasma cells can be visualized in simple terms as the cell acquires the ability to secrete the extracellular portion of its BCR in large quantities.

Antibody Classes

Antibodies can be divided into five classes—IgM, IgG, IgA, IgD, IgE—based on their physiochemical, structural, and immunological properties. IgGs, which make up about 80 percent of all antibodies, have heavy chains that consist of one variable domain and three identical constant domains. IgA and IgD also have three constant domains per heavy chain, whereas IgM and IgE each have four constant domains per heavy chain. The variable domain determines binding specificity and the constant domain of the heavy chain determines the immunological mechanism of action of the corresponding antibody class. It is possible for two antibodies to have the same binding specificities but be in different classes and, therefore, to be involved in different functions.

After an adaptive defense is produced against a pathogen, typically plasma cells first secrete IgM into the blood. BCRs on naïve B cells are of the IgM class and occasionally IgD class. IgM molecules make up approximately ten percent of all antibodies. Prior to antibody secretion, plasma cells assemble IgM molecules into pentamers (five individual antibodies) linked by a joining (J) chain, as shown in the figure below. The pentamer arrangement means that these macromolecules can bind ten identical antigens. However, IgM molecules released early in the adaptive immune response do not bind to antigens as stably as IgGs, which are one of the possible types of antibodies secreted in large quantities upon re-exposure to the same pathogen. The figure below summarizes the properties of immunoglobulins and illustrates their basic structures.

Table shows the structure and function of the five types of immunoglobulins: IgA, IgD, IgE, IgG and IgM. IgD, IgA and IgG all have a Y-shaped structure. IgD is part of the B cell receptor, and activates basophils and mast cells. IgE protects against parasitic worms, and is responsible for allergic reactions. IgG is secreted by plasma cells in the blood, and is able to cross the placenta into the fetus. IgA consist of two Y-shaped structures connected at their trunk. It is found in mucous, saliva, tears and breast milk, and protects against pathogens. IgM consists of five Y-shaped structures connected to a pentagram, with the top of the Ys facing out. It may be attached to the surface of B cells or secreted in the blood, and is responsible for the early stages of immunity.

Immunoglobulins have different functions, but all are composed of light and heavy chains that form a Y-shaped structure.

IgAs populate the saliva, tears, breast milk, and mucus secretions of the gastrointestinal, respiratory, and genitourinary tracts. Collectively, these bodily fluids coat and protect the extensive mucosa (4000 square feet in humans). The total number of IgA molecules in these bodily secretions is greater than the number of IgG molecules in the blood serum. A small amount of IgA is also secreted into the serum in monomeric form. Conversely, some IgM is secreted into bodily fluids of the mucosa. Similar to IgM, IgA molecules are secreted as polymeric structures linked with a J chain. However, IgAs are secreted mostly as dimeric molecules, not pentamers.

IgE is present in the serum in small quantities and is best characterized in its role as an allergy mediator. IgD is also present in small quantities. Similar to IgM, BCRs of the IgD class are found on the surface of naïve B cells. This class supports antigen recognition and maturation of B cells to plasma cells.

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