Abstract
The immunoglobulin repertoire is initially generated by the rearrangement of discrete gene segments encoding the heavy and light chains. Heavy chain genes are composed of a variable gene segment (VH), a diversity (D) gene segment and a joining (JH) gene segment, and kappa light chain genes contain variable (VK) and joining (JK) gene segments. In developing B cells, the gene segments are independently selected from pools of several hundred VH and VK gene segments, 12 D gene segments, and four JH or JK gene segments, creating a diverse population of immunoglobulins. The VH gene segments are grouped into nine subfamilies which contain gene segments that share 80% or greater homology, and span a region between 500 and 2500 kilobasepairs (kb) that is located several hundred kb upstream of the D and JH gene segments on chromosome 12 (Brodeur PH, Riblet R, 1984; Brodeur PH, 1987). VK gene segments have been grouped into at least 18 subfamilies and are located upstream of the JK gene segments on chromosome 6 (Potter M, et al, 1982). Addition and deletion of nucleotides at the junctions of the gene segments creates greater diversity in the third hypervariable region in each gene. The repertoire generated by gene rearrangements can be modified by interactions between immunoglobulins expressed on the B-cell surface and endogenous antigens leading to the expansion or inhibition of certain antibody specificities.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Bona C (1988) V Genes Encoding Autoantibodies: Molecular and Phenotypic Characteristics. Ann. Rev. Immunol. 6: 327–358.
Brodeur PH, Riblet R (1984) The Immunoglobulin Heavy Chain Variable Region (Igh-V) Locus in the Mouse I. One Hundred Igh-V Genes Comprise Seven Families of Homologous Genes. Eur J Immunology 14: 922–930.
Brodeur P (1987) Genes Encoding the Immunoglobulin Variable Regions. In: Calabi F, Neuberrger MS (eds) Molecular Genetics of Immunoglobulin. Elsevier Science Publishers, New York, 1987.
Cockerill PN, Garrard WT (1986) Chromosomal Loop Anchorage of the Kappa Immunoglobulin Gene Occurs next to the Enhancer in a Region Containing Topoisomerase II Sites. Cell 44: 273–282.
Desiderio SV, Yancopoulos GD, Paskind M, Thomas E, Boss MA, Landau N, Alt FW, Baltimore, D (1984) Insertion of N Regions into Heavy-chain Genes is Correlated with Expression of Terminal Deoxytransferase in B Cells. Nature 311: 752–755.
D’Hoostelaere LA, Huppi K, Mock B, Mallett C, Potter M (1988) The IgK Chain Allelic Groups Among the IgK Haplotypes and IgK Crossover Populations Suggest a Gene Order. J Immunology 141: 652–661.
Feddersen RM, Van Ness BG (1985) Double recombination of a single immunoglobulin K-chain allele: Implications for th mechanism of rearrangement. Proc Natl Acad Sci USA 82: 4793–4797.
Jeong HD, Teale JM (1988) Comparison of the Fetal and Adult Functional B Cell Repertoires by Analysis of VH Gene Family Expression. J Exp Med 168: 589–603.
Lawler AM, Lin PS, Gearhart, PJ (1987) Adult B-cell reperotire is biased toward two heavy-chain variable-region genes that rearrange frequently in fetal pre-B cells. Proc Natl Acad Sci USA 84: 2454–2458.
Lewis S, Rosenberg N, Alt W, Baltimore D (1982) Continuing Kappa-Gene Rearrangement in a Cell Line Transformed by Abelson Murine Leukemia Virus. Cell 30: 807–816.
Perlmutter RM, Kearney JF, Chang S, Hood LE (1985) Developmentally Controlled Expression of Immunoglobulin VH Genes. Science 227: 1597–1600.
Potter M, Newell JB, Rudikoff S, Haber E (1982) Classification of Mouse VK Groups Based on the Partial Amino Acid Sequence to the First Invariant Tryptophan: Impact of 14 New Sequences from IgG Myeloma Proteins. Molecular Immunology 19: 1619–1630.
Reth MG, Jackson S, Alt FW (1986) VHDJH Formation and DJH replacement During Pre-B Differentiation: Non-random Usage of Gene Segments. EMBO J. 5: 2131–2138.
Shapiro MA, Weigert M (1987) How Immunoglobulin VK Genes Rearrange. J Immunology 139: 3834–3839.
Wu GE, Paige CJ (1986) VH Gene Family Utilization in Colonies Derived from B and Pre-B Cells Detected by the RNA Colony Blot Assay. EMBO J 5: 3475–3481.
Yancopoulos GD, Desiderio SV, Paskind M, Kearney JF, Baltimore D, Alt FW (1984) Preferential Utilization of the Most JH-proximal VH Gene Segments in Pre-B-cell Lines. Science 311: 727–733.
Yancopoulos GD, Malynn BA, Alt FW (1988) Developmentally Regulated and Strain-specific Expression of Murine VH Gene Families. J Exp Med 168: 417–435.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1990 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Lawler, A., Gearhart, P. (1990). Immunoglobulin Kappa Variable Gene Segment Usage during Ontogeny. In: Demaine, A.G., Banga, JP., McGregor, A.M. (eds) The Molecular Biology of Autoimmune Disease. NATO ASI Series, vol 38. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-75133-2_2
Download citation
DOI: https://doi.org/10.1007/978-3-642-75133-2_2
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-75135-6
Online ISBN: 978-3-642-75133-2
eBook Packages: Springer Book Archive