Immunoglobulin Gene Construction: Human

Alexander H Lucas, Children's Hospital Oakland Research Institute, Oakland, California, USA

Published online: May 2003

DOI: 10.1038/npg.els.0001172

Human immunoglobulin genes exist as tandem arrays of gene segments that undergo somatic recombination and hypermutation during B-lymphocyte development. Together, these processes enable the generation of a vast repertoire of immunoglobulin molecules capable of recognizing and eliminating infectious agents.

Keywords: antibody; immunoglobulin; variable region; constant region; somatic recombination; hypermutation

Figure 1. An immunoglobulin G (IgG) molecule.
Figure 2. Genomic organization of human immunoglobulin genes. (a) Light chain locus (chromosome 2); (b) light chain locus (chromosome 22); (c) heavy chain locus (chromosome 14). Coding sequences are indicated by open boxes. Nonfunctional or pseudogenes are indicated by shading. Arrows indicate transcriptional polarity. Not drawn to scale.
Figure 3. L chain production. The process of antigen-independent gene rearrangement that generates a functional L chain gene. A complete VL coding region is created by recombination between the V1 gene segment and J3. Splicing of the primary transcript from the V1-J3-C assemblage generates an mRNA in which the V and C regions are contiguous.
Figure 4. H chain production. The process of antigen-independent gene rearrangement that generates a functional H chain gene. A complete VH coding region is created by recombination between the V2 gene segment, D3 and J4. Splicing of the primary transcript from the V2-D3-J4-C assemblage generates an mRNA in which the V and C regions are contiguous.
Figure 5. Generation of membrane and secreted forms of immunoglobulin M (IgM). The C gene is divided into exons (boxes) and introns (lines). The primary transcript generated from a rearranged H locus contains intron sequences and exon sequences encoding the signal or leader peptide (L), the assembled V region (VDJ), the four C domains, the secreted (s) and membrane (m) termini. The transcript is differentially processed to generate a mature mRNA having either the secreted terminus or the membrane terminus. The introns are removed during processing such that the exons are contiguous.
Figure 6. Class switching. Rearrangements in the H locus occur in the B cell following antigen stimulation. A VDJ module switches from C to C1 by site-specific recombination at switch (S) regions. Looping out of the intervening DNA occurs during this process, resulting in the deletion of CH genes. A subsequent switch occurs, resulting in the relocation of the VDJ module to the C2 gene.
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 References
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 Further Reading
    book Honjo T and Alt FW (1995) Immunoglobulin Genes, 2nd edn. New York: Academic Press.
    book Max EE (1999) "Immunoglobulins: molecular genetics". Paul WE Fundamental Immunology, 4th ed., pp. 111–182. Philadelphia: Lippincott-Raven
    book Podolsky SH and Tauber AI (1997) The Generation of Diversity: Clonal Selection Theory and the Rise of Molecular Immunology. Cambridge, MA: Harvard University Press.
    Williams AF and Barclay AN (1988) The immunoglobulin superfamily - domains for cell surface recognition. Annual Review of Immunology 6: 381–405.

Related Sub-Topics:

Immunoregulation | Acquired (Adaptive) Immunity | Antibodies | Molecular Genetics of Common and Complex Disease | Mutational Mechanisms of Genetic Disease | Gene and Genome Structure and Organisation | Inter-Individual Variation and Polymorphism | Epigenetics and Disease | Transcription of DNA | Transcriptional Regulation | DNA Structure and Function | Posttranscriptional Modification | Evolution of Coding and Functional Modules
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Article Title: Immunoglobulin Gene Construction: Human
 
How to Cite close
Lucas, Alexander H(May 2003) Immunoglobulin Gene Construction: Human. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0001172]