Fig. 5.18 Deletion of the TCRδ locus is induced by rearrangement of a Vα to Jα gene segment. The TCRδ locus is entirely contained within the chromosomal region containing the TCRα locus. When any V region in the Vα/Vδ region rearranges to any one of the Jα segments, the intervening region, and the entire Vδ locus, is deleted. Thus, Vα rearrangement prevents any continued expression of a Vδ gene and precludes lineage development down the γ:δ pathway.
naive B cells express both Cμ and Cδ isotypes at the same time and how the same antibody gene can generate both membrane-bound immunoglobulin and secreted immunoglobulin through alternative mRNA splicing. During an antibody response, activated B cells can switch to the expression of CH genes other than Cμ and Cδ by a type of somatic recombination known as class switching (discussed in Chapter 10) that links different heavy-chain C regions (CH) to the rearranged VDJH gene segment.
5-12 Different classes of immunoglobulins are distinguished by the structure of their heavy-chain constant regions.
The five main classes of immunoglobulins are IgM, IgD, IgG, IgE, and IgA, all of which can occur as transmembrane antigen receptors or secreted antibodies (Fig. 5.19). In humans, IgG is found as four subclasses (IgG1, IgG2, IgG3, and IgG4), named by decreasing order of their abundance in serum, and IgA antibodies are found as two subclasses (IgA1 and IgA2). The different heavy chains that define these classes are known as isotypes and are designated by the lowercase Greek letters μ, δ, γ, ε, and α. The different heavy chains are encoded by different immunoglobulin CH genes located in a gene cluster that is 3ʹ of the JH segments as illustrated in Fig. 5.19. Figure 5.20 lists the major physical and functional properties of the different human antibody classes.
The functions of the immunoglobulin classes are discussed in detail in Chapter 10, in the context of the humoral immune response; here, we just touch on them briefly. IgM is the first class of immunoglobulin produced after activation of a B cell, and the IgM antibody is secreted as a pentamer (see Section 5-14 and Fig. 5.21). This accounts for the high molecular weight of IgM and the fact that it is normally present in the bloodstream but not in tissues. Being a pentamer
The general structure of the main immunoglobulin isotypes (above in upper panel) is indicated, with each rectangle denoting an immunoglobulin domain. These isotypes are encoded by separate heavy-chain C-region genes arranged in a cluster in both mouse and human (lower panel). The constant region of the heavy chain for each isotype is indicated by the same color as the C-region gene segment that encodes it. IgM and IgE lack a hinge region but each contains an extra heavy-chain domain. Note the differences in the number and location of the disulfide bonds (black lines) linking the chains. The isotypes also differ in the distribution of N-linked carbohydrate groups, shown as hexagons. In humans, the gene cluster shows evidence of evolutionary duplication of a unit consisting of two γ genes, an ε gene, and an α gene. One of the ε genes is a pseudogene (ψ); hence only one subtype of IgE is expressed. For simplicity, other pseudogenes are not illustrated, and the exon details within each C gene are not shown. The classes of immunoglobulins found in mice are called IgM, IgD, IgG1, IgG2a, IgG2b, IgG3, IgA, and IgE.