Immunoglobulin Gene Construction: Human

Abstract

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) κ Light chain locus (chromosome 2); (b) λ 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‐Cκ 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‐Cμ 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 Cμ 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 Cμ 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 Cμ to Cγ1 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 Cα2 gene.

close

References

Dreyer WJ and Bennett JC (1965) The molecular basis of antibody formation: a paradox. Proceedings of the National Academy of Sciences of the USA 54: 864–869.

Hilschmann N and Craig LC (1965) Amino acid sequence studies with Bence‐Jones proteins. Proceedings of the National Academy of Sciences of the USA 53: 1403–1409.

Koshland ME, Davis JJ and Fujita NJ (1969) Evidence for multiple gene control of a single polypeptide chain: the heavy chain of rabbit immunoglobulin. Proceedings of the National Academy of Sciences of the USA 63: 1274–1281.

Litman GW, Anderson MK and Rast JP (1999) Evolution of antigen binding receptors. Annual Review of Immunology 17: 109–147.

Tonegawa S, Hozumi N, Matthyssens G and Schuller R (1975) Somatic changes in the content and context of immunoglobulin genes. Cold Spring Harbor Symposia on Quantitative Biology 41: 877–888.

Weigert M, Cesari IM, Yonkovich SJ and Cohn M (1970) Variability in the lambda light chains sequences of mouse antibody. Nature 228: 1045–1047.

Further Reading

Honjo T and Alt FW (1995) Immunoglobulin Genes, 2nd edn. New York: Academic Press.

Max EE (1999) Immunoglobulins: molecular genetics. Paul WE Fundamental Immunology, 4th ed., pp. 111–182. Philadelphia: Lippincott‐Raven

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.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

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]