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Science 24 March 1995:
Vol. 267. no. 5205, pp. 1825 - 1828
DOI: 10.1126/science.7892607
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Articles

Science, Vol 267, Issue 5205, 1825-1828
Copyright © 1995 by American Association for the Advancement of Science

articles

Switch transcripts in immunoglobulin class switching

M Lorenz, S Jung, and A Radbruch

Institute for Genetics, University of Cologne, Germany.

B cells can exchange gene segments for the constant region of the immunoglobulin heavy chain, altering the class and effector function of the antibodies that they produce. Class switching is directed to distinct classes by cytokines, which induce transcription of the targeted DNA sequences. These transcripts are processed, resulting in spliced "switch" transcripts. Switch recombination can be directed to immunoglobulin G1 (IgG) by the heterologous human metallothionein IIA promoter in mutant mice. Induction of the structurally conserved, spliced switch transcripts is sufficient to target switch recombination to IgG1, whereas transcription alone is not.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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Replacement of I{gamma}3 germ-line promoter by I{gamma}1 inhibits class-switch recombination to IgG3.
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The in vivo pattern of AID targeting to immunoglobulin switch regions deduced from mutation spectra in msh2-/- ung-/- mice.
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Germ line transcription in mice bearing neor gene downstream of I{gamma}3 exon in the Ig heavy chain locus.
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AID-dependent histone acetylation is detected in immunoglobulin S regions.
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J. Exp. Med. 203, 215-226
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Germline Transcription and Switch Recombination of a Transgene Containing the Entire H Chain Constant Region Locus: Effect of a Mutation in a STAT6 Binding Site in the {gamma}1 Promoter.
W. A. Dunnick, J. Shi, K. A. Graves, and J. T. Collins (2004)
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Endogenous Expression of Activation-Induced Cytidine Deaminase in Cell Line WEHI-231.
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DNA Acrobats of the Ig Class Switch.
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X. Chen, K. Kinoshita, and T. Honjo (2001)
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Quantitative Regulation of Class Switch Recombination by Switch Region Transcription.
C.-G. Lee, K. Kinoshita, A. Arudchandran, S. M. Cerritelli, R. J. Crouch, and T. Honjo (2001)
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D. L. Chalker and M.-C. Yao (2001)
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Evidence for Class-specific Factors in Immunoglobulin Isotype Switching.
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Normal Isotype Switching in B Cells Lacking the I{micro} Exon Splice Donor Site: Evidence for Multiple I{micro}-Like Germline Transcripts.
I. I. Kuzin, G. D. Ugine, D. Wu, F. Young, J. Chen, and A. Bottaro (2000)
J. Immunol. 164, 1451-1457
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Regulated Genomic Instability and Neoplasia in the Lymphoid Lineage.
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Switching to IgG3, IgG2b, and IgA Is Division Linked and Independent, Revealing a Stochastic Framework for Describing Differentiation.
E. K. Deenick, J. Hasbold, and P. D. Hodgkin (1999)
J. Immunol. 163, 4707-4714
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The Ig heavy chain intronic enhancer core region is necessary and sufficient to promote efficient class switch recombination.
E. Sakai, A. Bottaro, and F. W. Alt (1999)
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Switch Recombination in a Transfected Plasmid Occurs Preferentially in a B Cell Line That Undergoes Switch Recombination of Its Chromosomal Ig Heavy Chain Genes.
J. Stavnezer, S. P. Bradley, N. Rousseau, T. Pearson, A. Shanmugam, D. J. Waite, P. R. Rogers, and A. L. Kenter (1999)
J. Immunol. 163, 2028-2040
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Specific Expression of Activation-induced Cytidine Deaminase (AID), a Novel Member of the RNA-editing Deaminase Family in Germinal Center B Cells.
M. Muramatsu, V. S. Sankaranand, S. Anant, M. Sugai, K. Kinoshita, N. O. Davidson, and T. Honjo (1999)
J. Biol. Chem. 274, 18470-18476
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An extrachromosomal switch recombination substrate reveals kinetics and substrate requirements of switch recombination in primary murine B cells.
K. Petry, G. Siebenkotten, R. Christine, K. Hein, and A. Radbruch (1999)
Int. Immunol. 11, 753-763
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The Evolutionarily Conserved Sequence Upstream of the Human Ig Heavy Chain S{gamma}3 Region Is an Inducible Promoter: Synergistic Activation by CD40 Ligand and IL-4 Via Cooperative NF-{kappa}B and STAT-6 Binding Sites.
A. Schaffer, A. Cerutti, S. Shah, H. Zan, and P. Casali (1999)
J. Immunol. 162, 5327-5336
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Position-dependent inhibition of class-switch recombination by PGK-neor cassettes inserted into the immunoglobulin heavy chain constant region locus.
K. J. Seidl, J. P. Manis, A. Bottaro, J. Zhang, L. Davidson, A. Kisselgof, H. Oettgen, and F. W. Alt (1999)
PNAS 96, 3000-3005
   Abstract »    Full Text »    PDF »
Molecular Mechanism of Immunoglobulin Class Switch Recombination.
K. KINOSHITA, C.-G. LEE, J. TASHIRO, M. MURAMATSU, X.-C. CHEN, K. YOSHIKAWA, and T. HONJO (1999)
Cold Spring Harb Symp Quant Biol 64, 217-226
   Abstract »    PDF »
I{alpha} exon-replacement mice synthesize a spliced HPRT–C{alpha} transcript which may explain their ability to switch to IgA. Inhibition of switching to IgG in these mice.
G. Qiu, G. R. Harriman, and J. Stavnezer (1999)
Int. Immunol. 11, 37-46
   Abstract »    Full Text »    PDF »
Processing of Switch Transcripts Is Required for Targeting of Antibody Class Switch Recombination.
K. Hein, M. G.O. Lorenz, G. Siebenkotten, K. Petry, R. Christine, and A. Radbruch (1998)
J. Exp. Med. 188, 2369-2374
   Abstract »    Full Text »    PDF »
CBF{alpha}3 (AML2) Is Induced by TGF-{beta}1 to Bind and Activate the Mouse Germline Ig {alpha} Promoter.
M.-J. Shi and J. Stavnezer (1998)
J. Immunol. 161, 6751-6760
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Class Switching in B Cells Lacking 3' Immunoglobulin Heavy Chain Enhancers.
J. P. Manis, N. van der Stoep, M. Tian, R. Ferrini, L. Davidson, A. Bottaro, and F. W. Alt (1998)
J. Exp. Med. 188, 1421-1431
   Abstract »    Full Text »    PDF »
Localization of Splenic B Cells Activated for Switch Recombination by In Situ Hybridization with I{gamma}1 Switch Transcript and Rad51 Probes.
M.-C. Peakman and N. Maizels (1998)
J. Immunol. 161, 4008-4015
   Abstract »    Full Text »    PDF »
Overexpression of BSAP/Pax-5 Inhibits Switching to IgA and Enhances Switching to IgE in the I.29{micro} B Cell Line.
G. Qiu and J. Stavnezer (1998)
J. Immunol. 161, 2906-2918
   Abstract »    Full Text »    PDF »
The Ability of CD40L, but Not Lipopolysaccharide, To Initiate Immunoglobulin Switching to Immunoglobulin G1 Is Explained by Differential Induction of NF-kappa B/Rel Proteins.
S.-C. Lin, H. H. Wortis, and J. Stavnezer (1998)
Mol. Cell. Biol. 18, 5523-5532
   Abstract »    Full Text »
Efficient Recombination of a Switch Substrate Retrovector in CD40-Activated B Lymphocytes: Implications for the Control of CH Gene Switch Recombination.
J. Ballantyne, D. L. Henry, J. R. Muller, F. Briere, C. M. Snapper, M. Kehry, and K. B. Marcu (1998)
J. Immunol. 161, 1336-1347
   Abstract »    Full Text »    PDF »
Generation of Switch Hybrid DNA Between Ig Heavy Chain-{micro} and Downstream Switch Regions in B Lymphocytes.
J. R. Muller, T. Giese, D. L. Henry, J. F. Mushinski, and K. B. Marcu (1998)
J. Immunol. 161, 1354-1362
   Abstract »    Full Text »    PDF »
STAT6 Is Required for IL-4-Induced Germline Ig Gene Transcription and Switch Recombination.
L. A. Linehan, W. D. Warren, P. A. Thompson, M. J. Grusby, and M. T. Berton (1998)
J. Immunol. 161, 302-310
   Abstract »    Full Text »    PDF »
T Helper 1 (Th1) and Th2 Characteristics Start to Develop During T Cell Priming and Are Associated with an Immediate Ability to Induce Immunoglobulin Class Switching.
K.-M. Toellner, S. A. Luther, D. M.-Y. Sze, R. K.-W. Choy, D. R. Taylor, I. C.M. MacLennan, and H. Acha-Orbea (1998)
J. Exp. Med. 187, 1193-1204
   Abstract »    Full Text »    PDF »
Nucleolin is one component of the B cell-specific transcription factor and switch region binding protein, LR1.
L. A. Hanakahi, L. A. Dempsey, M.-J. Li, and N. Maizels (1997)
PNAS 94, 3605-3610
   Abstract »    Full Text »    PDF »
The Promotion of  V Region Hypermutation.
M. D. Scharff, V. Poltoratsky, and N. S. Green (1997)
J. Exp. Med. 185, 185-188
   Full Text »    PDF »


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