Immunoglobulins, also known as antibodies, are glycoprotein molecules produced by plasma cells (white blood cells). They act as a critical part of the immune response by specifically recognizing and binding to particular antigens, such as bacteria or viruses, and aiding in their destruction. The antibody immune response is highly complex and exceedingly specific. The various immunoglobulin classes and subclasses (isotypes) differ in their biological features, structure, target specificity, and distribution. Hence, the assessment of the immunoglobulin isotype can provide useful insight into the complex humoral immune response. Assessment and knowledge of immunoglobulin structure and classes is also important for selection and preparation of antibodies as tools for immunoassays and other detection applications.

Explore antibodies  Immunoglobulin structure and classes

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Soluble vs. membrane-bound immunoglobulins

Immunoglobulins occur in two main forms: soluble antibodies and membrane-bound antibodies (the latter contain a hydrophobic transmembrane region). Alternative splicing regulates the production of secreted antibodies and surface-bound B cell receptors in B cells.

Membrane-bound immunoglobulins are associated non-covalently with two accessory peptides, forming the B-cell antigen receptor complex. The first antigen receptors expressed by B cells are IgM and IgD. The receptor is a prototype of the antibody that the B cell is prepared to produce. The B cell receptor (BCR) can only bind antigens. It is the heterodimer of Ig alpha and Ig beta that enables the cell to transduce the signal and respond to the presence of antigens on the cell surface. The signal generated causes the growth and proliferation of the B cell and antibody production inside the plasma cell.

Immunoglobulin classes (isotypes)

The various antibodies produced by plasma cells are classified by isotype, each of which differs in function and antigen responses primarily due to structure variability. Five major antibody classes have been identified in placental mammals: IgA, IgD, IgE, IgG, and IgM. This classification is based on differences in amino acid sequence in the constant region (Fc) of the antibody heavy chains. IgG and IgA are further grouped into subclasses (e.g., in human IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2) based on additional small differences in the amino acid heavy chain sequences.

Based on differences in the amino acid sequence in the constant region of the light chain, immunoglobulins can be further sub-classified by determination of the type of light chain (kappa light chain or lambda light chain). A light chain has two successive domains: one constant domain and one variable domain. The ratio of these two light chains differs greatly among species, but the light chains are always either both kappa or both lambda, never one of each.

Determination of individual subclasses is relevant in assessing primary immunodeficiencies or immune responses, especially if the total IgG or IgA concentration is not altered or elevated.

Isotype class switching

One of the primary functions of B cells in adaptive immunity is that of effecting a humoral response through the secretion of specific antibodies to address invading bodies and their toxic products. Some of these cells can undergo a “class switch” that causes expression of a new antibody isotype. For example, the antibody isotype could switch from an IgM to an antibody of all possible classes (e.g., IgG1,...IgG4, IgE). During this switch, the constant region of the heavy chain is changed, but not the variable region of the heavy chain. This switch does not affect the antibody’s specificity for its antigen, but it does alter the effector functions that each class of antibody can execute. The antibody class switch is critically dependent on the type of cytokine that is present. Various cytokines, such as IL-4, IL-5, IFN-gamma, and TGF-beta, are known to be responsible for class switching. At a certain stage, the cell will lose its ability to undergo a switch to a class that has been generated before.

Why knowing the isotype matters

Immune responses can vary with each antigen presented to the immune system, so quantifying specific antibody levels helps to interpret the immune response after immunization or vaccination.

Assessing human monoclonal antibody levels is also used widely as a diagnostic indicator to determine immunoglobulin-deficiency disorders, such as autoimmune diseases and gastrointestinal conditions that can be characterized by specific isotype deficiencies or varying concentrations of one or more isotypes. Disease states can range from the absence of one isotype class or subclass to a total deficiency of immunoglobulin classes.

The various isotypes also differ in their ability to bind to certain resins. Knowing the isotype is essential to assess the optimal purification techniques in order to gain maximum yield and purity of a desired antibody.

Human immunoglobulins and their properties.
 ImmunoglobulinSerum level 
Molecular mass 
Activation/Binding of complementHalf-life 
HumanIgA10.6–3160 (monomer)-5.5 
HumanIgA20.06–0.6160 (monomer)-5.5
HumanIgM1.5970 (pentamer)+++5–10
HumanIgE5 x 10-5188-2
HumanIgG30.2–1.7165 +++7

+++ = Very strong affinity; ++ = Strong affinity; + = Moderate affinity; - = No affinity        

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