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===Immunoglobulin Class Switching===
 
===Immunoglobulin Class Switching===
Different classes of antibody differ from each other in size, charge, amino acid composition, associated carbohydrate and function. Immunoglobulin heavy and light chains are encoded by separate genes with the first 300 bases of each gene encoding the variable part of each protein chain. The combination of the VH and VL contribute to the antigenic specificity and any individual has the capability of producing over 100 million different antibody specificities. The rest of the antibody gene encodes all the constant domains. There are four different types of heavy chain constant domains - μ, γ, ε, α. Different heavy chains are associated with different classes of antibody;
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Different classes of antibody differ from each other in size, charge, amino acid composition, associated carbohydrate and function. Immunoglobulin heavy and light chains are encoded by separate genes with the first 300 bases of each gene encoding the variable part of each protein chain. The combination of the VH and VL contribute to the antigenic specificity and any individual has the capability of producing over 100 million different antibody specificities. The rest of the antibody gene encodes all the constant domains. There are five different types of heavy chain constant domains - μ, γ, ε, α. Different heavy chains are associated with different classes of antibody;
 
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* '''&mu; chain - [[IgM]] '''
 
* '''&mu; chain - [[IgM]] '''
 
* '''&gamma; chain -[[IgG]]'''
 
* '''&gamma; chain -[[IgG]]'''
 
* '''&epsilon; chain - [[IgE]]'''
 
* '''&epsilon; chain - [[IgE]]'''
* '''&alpha; chain - [[IgA]]'''  
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* '''&alpha; chain - [[IgA]]'''
 
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In humans and mice there exists a fifth Ig class, '''[[IgD]] (δ chain)'''. IgD is always expressed on B-cell membranes with [[IgM]] but is ''never secreted''. The sequence of constant region genes on the chromosome is M, G, E and A. In humans/ rodents the Cδ ([[IgD]]) is immediately downstream of the M gene and prior to antigenic stimulation, B-cells express cell membrane-associated [[IgM]]. The first immunoglobulin produced during an immune response is '''always [[IgM]]''' because the Cμ gene is the first constant H chain gene downstream of the variable domain. After antigenic exposure the [[IgM]]+ B-cells differentiate and begin to synthesise other classes of immunoglobulin, but only under the '''direct influence of a T-cell'''. This system is known as '''immunoglobulin heavy chain switching'''. The [[IgG]] antibodies produced in both primary and secondary responses originate from the same clones of B-cells as the [[IgM]] antibodies. The different antibody classes have the same variable domain combinations, and therefore the same antigenic specificity. Under the influence of T-cells, B-cells undergo immunoglobulin heavy chain switching and the B-cells mature from [[IgM]] to [[IgG]] producers and IgE and IgA producers can also be generated. These immunoglobulins tend to be produced within lymphoid tissue associated with mucosal surfaces.
 
In humans and mice there exists a fifth Ig class, '''[[IgD]] (δ chain)'''. IgD is always expressed on B-cell membranes with [[IgM]] but is ''never secreted''. The sequence of constant region genes on the chromosome is M, G, E and A. In humans/ rodents the Cδ ([[IgD]]) is immediately downstream of the M gene and prior to antigenic stimulation, B-cells express cell membrane-associated [[IgM]]. The first immunoglobulin produced during an immune response is '''always [[IgM]]''' because the Cμ gene is the first constant H chain gene downstream of the variable domain. After antigenic exposure the [[IgM]]+ B-cells differentiate and begin to synthesise other classes of immunoglobulin, but only under the '''direct influence of a T-cell'''. This system is known as '''immunoglobulin heavy chain switching'''. The [[IgG]] antibodies produced in both primary and secondary responses originate from the same clones of B-cells as the [[IgM]] antibodies. The different antibody classes have the same variable domain combinations, and therefore the same antigenic specificity. Under the influence of T-cells, B-cells undergo immunoglobulin heavy chain switching and the B-cells mature from [[IgM]] to [[IgG]] producers and IgE and IgA producers can also be generated. These immunoglobulins tend to be produced within lymphoid tissue associated with mucosal surfaces.
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