Abstract
The seven antigen receptor loci are targeted for V(D)J recombination at different times, different developmental stages, and with B or T lineage specificity by unknown mechanisms. The physical basis for the differential accessibility in this site-specific recombination reaction has been a matter of much speculation. Possibilities have included the processes of transcription (Ferrier et al., 1989; Martin et al., 1991; Schlissel et al., 1991) and DNA replication, and the structural features of DNA methylation and chromatin structure (Mather and Perry, 1983; Persiani and Selsing, 1989; Storb and Arp, 1983; Yancopoulos et al., 1986). The relevant order and hierarchy of these parameters in controlling accessibility of the V(D)J recombination activity are unknown. Although some studies have raised the possibility that transcription is a requirement for recombination, the temporal resolution of such studies has been limiting. They have not permitted determination of whether transcription and recombination are consequences of a common chromatin change or whether transcription precedes and, thereby, activates recombination.
This is a preview of subscription content, log in via an institution to check access.
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
Alt, F. W., Blackwell, T. K., and Yancopoulos, G. D. (1987). Development of the primary antibody repertoire. Science 238, 1079–1087.
Ferrier, P., Covey, L. R., Suh, H., Winoto, A., Hood, L., and Alt, F. W. (1991). T cell receptor DJ but not VDJ rearrangement within a recombination substrate introduced into a pre-B cell line. Int. Immunol. 1, 66–74.
Gauss, G., and Lieber, M. R. (1992). The basis for the mechanistic bias for deletional over inversional V(D)J recombination. Genes Dev. 6(8), in press.
Hendrickson, E. A., Liu, V. F., and Weaver, D. T. (1991). Strand breaks without DNA rearrangement in V(D)J recombination. Mol. Cell. Biol. 11, 3155–3162.
Hesse, J. E., Lieber, M. R., Mizuuchi, K., and Geliert, M. (1987). Extrachromosomal DNA substrates in pre-B cells undergo inversion or deletion at immunoglobulin V-(D)-J joining signals. Cell 49, 775–783.
Hesse, J. E., Lieber, M. R., Mizuuchi, K., and Geliert, M. (1989). V(D)J recombination: a functional definition of the joining signals. Genes Dev. 3, 1053–1061.
Hsieh, C.-L., McCloskey, R. P., Radany, E., and Lieber, M. R. (1991). V(D)J recombination: evidence that a replicative mechanism is not required. Mol. Cell. Biol. 11, 3972–3977.
Hsieh, C.-L. and Lieber, M.R. (1992). CpG methylated minichromosomes become inaccessible for V(D)J recombination after undergoing replication. EMBO J. 11, 315–325.
Hsieh, C.-L., McCloskey, R. P., and Lieber, M. R. (1992). V(D)J recombination is not affected by transcription. J. Biol. Chem. 267 (in press).
Ichihara, Y., Matsuoka, H., and Kurosawa, Y. (1988). Organization of human immunoglobulin heavy chain diversity gene loci. EMBO J. 7, 4141–4150.
Kabat, E., Wu, T., Reid-Miller, M., Perry, H., and Gottesm N, K. (1987) Sequences of Proteins of Immunological Interest, 4th Ed., U.S. Dept. HHS, Washington, D.C..
Kurosawa, Y. and Tonegawa, S. (1982). Organization, structure, and assembly of immunoglobulin heavy-chain diversity DNA segments. J. Exp. Med. 155, 201–218.
Lewis, S. M., Hesse, J. E., Mizuuchi, K., and Geliert, M. (1988). Novel strand exchanges in V(D)J recombination. Cell 55, 1099–1107.
Lieber, M. R., Hesse, J. E. Mizuuchi, K., and Geliert, M. (1987). Developmental stage specificity of the lymphoid V(D)J recombination activity. Genes Dev. 1, 751–761.
Lieber, M.R. (1991). Site-specific recombination in the immune system. FASEB J. 5(14), 934–2944.
Martin, D., Huang, R., LeBien, T., and Van Ness R. (1991). Induced rearrangement of k genes in the BLIN-1 human pre-B cell line correlates with germline J-Ck and Vk transcription. J. Exp. Med. 173, 639–645.
Mather, E. L., and Perry, R. P. (1983). Methylation status and DNasel sensitivity of immunoglobulin genes: changes associated with rearrangement. Proc. Natl. Acad. Sci. USA 80, 4689–4693.
Meek, K., Hasemann, C., and Capra, J.D. (1989). Novel rearrangements at the immunoglobulin D locus. J. Exp. Med. 170, 39–57.
Persiani, D. M., and Selsing, E. (1989). DNasel sensitivity of immunoglobulin light chain genes in Abelson murine leukemia virus transformed pre-B cell lines. Nucl. Acids Res. 17, 5339–5348.
Schlissel, M. S., Corcoran, L. M., and Baltimore, D. (1991). Virus-transformed pre-B cells show ordered activation but not inactivation of Immunoglobulin gene rearrangement and transcription. J. Exp. Med. 173, 711–720.
Storb, U. and Arp, B. (1983). Methylation patterns of Immunoglobulin genes in lymphoid cells: correlation of expression and differentiation with undermethylation. Proc. Natl. Acad. Sci. USA 80, 6642–6646.
Storb, U., Haasch, D., Arp, B., Sanchez, P., Cazenave, P., and Miller, J. (1989). Physical linkage of mouse lambda genes by pulsed-field gel electrophoresis suggests that the rearrangement process favors proximate target sequences. Mol. Cell. Biol. 9, 711–718.
Yancopoulos, G. D., Blackwell, T. K., Suh, H., Hood, L., and Alt, F. W. (1986). Introduced T cell receptor variable region gene segments recombine in pre-B cells: evidence that B and T cells use a common recombinase. Cell 44, 251–259.
Yancopoulos, G., Malynn, B., and Alt, F. (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
© 1992 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Hsieh, CL., Gauss, G., Lieber, M.R. (1992). Replication, Transcription, CpG Methylation and DNA Topology in V(D)J Recombination. In: Potter, M., Melchers, F. (eds) Mechanisms in B-Cell Neoplasia 1992. Current Topics in Microbiology and Immunology, vol 182. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-77633-5_15
Download citation
DOI: https://doi.org/10.1007/978-3-642-77633-5_15
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-77635-9
Online ISBN: 978-3-642-77633-5
eBook Packages: Springer Book Archive