The Mu Switch Region Tandem Repeats Are Important, but Not Required, for Antibody Class Switch Recombination

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2001 Jan 20

PMID 11148220

Citations 41

Authors

T M Luby

C E Schrader

J Stavnezer

E Selsing

Affiliations

Soon will be listed here.

Abstract

Class switch DNA recombinations change the constant (C) region of the antibody heavy (H) chain expressed by a B cell and thereby change the antibody effector function. Unusual tandemly repeated sequence elements located upstream of H chain gene exons have long been thought to be important in the targeting and/or mechanism of the switch recombination process. We have deleted the entire switch tandem repeat element (S(mu)) from the murine (mu) H chain gene. We find that the S(mu) tandem repeats are not required for class switching in the mouse immunoglobulin H-chain locus, although the efficiency of switching is clearly reduced. Our data demonstrate that sequences outside of the S(mu) tandem repeats must be capable of directing the class switch mechanism. The maintenance of the highly repeated S(mu) element during evolution appears to reflect selection for a highly efficient switching process rather than selection for a required sequence element.

Citing Articles

Generating and repairing genetically programmed DNA breaks during immunoglobulin class switch recombination.

Nicolas L, Cols M, Choi J, Chaudhuri J, Vuong B F1000Res. 2018; 7:458.

PMID: 29744038 PMC: 5904731. DOI: 10.12688/f1000research.13247.1.

Double-stranded DNA break polarity skews repair pathway choice during intrachromosomal and interchromosomal recombination.

Ling A, So C, Le M, Chen A, Hung L, Martin A Proc Natl Acad Sci U S A. 2018; 115(11):2800-2805.

PMID: 29472448 PMC: 5856553. DOI: 10.1073/pnas.1720962115.

A transcriptional serenAID: the role of noncoding RNAs in class switch recombination.

Yewdell W, Chaudhuri J Int Immunol. 2017; 29(4):183-196.

PMID: 28535205 PMC: 5890902. DOI: 10.1093/intimm/dxx027.

Mutations, kataegis and translocations in B cells: understanding AID promiscuous activity.

Casellas R, Basu U, Yewdell W, Chaudhuri J, Robbiani D, Di Noia J Nat Rev Immunol. 2016; 16(3):164-76.

PMID: 26898111 PMC: 4871114. DOI: 10.1038/nri.2016.2.

Interplay between Target Sequences and Repair Pathways Determines Distinct Outcomes of AID-Initiated Lesions.

Chen Z, Eder M, Elos M, Viboolsittiseri S, Chen X, Wang J J Immunol. 2016; 196(5):2335-47.

PMID: 26810227 PMC: 4760233. DOI: 10.4049/jimmunol.1502184.

References

Baar J, Pennell N, Shulman M . Analysis of a hot spot for DNA insertion suggests a mechanism for Ig switch recombination. J Immunol. 1996; 157(8):3430-5. View

Rolink A, Melchers F, Andersson J . The SCID but not the RAG-2 gene product is required for S mu-S epsilon heavy chain class switching. Immunity. 1996; 5(4):319-30. DOI: 10.1016/s1074-7613(00)80258-7. View

Du J, Zhu Y, Shanmugam A, Kenter A . Analysis of immunoglobulin Sgamma3 recombination breakpoints by PCR: implications for the mechanism of isotype switching. Nucleic Acids Res. 1997; 25(15):3066-73. PMC: 146845. DOI: 10.1093/nar/25.15.3066. View

Ballantyne J, Henry D, Marcu K . Antibody class switch recombinase activity is B cell stage specific and functions stochastically in the absence of 'targeted accessibility' control. Int Immunol. 1997; 9(7):963-74. DOI: 10.1093/intimm/9.7.963. View

Wuerffel R, Du J, Thompson R, Kenter A . Ig Sgamma3 DNA-specifc double strand breaks are induced in mitogen-activated B cells and are implicated in switch recombination. J Immunol. 1997; 159(9):4139-44. View

Mussmann R, Courtet M, Schwager J, Du Pasquier L . Microsites for immunoglobulin switch recombination breakpoints from Xenopus to mammals. Eur J Immunol. 1997; 27(10):2610-9. DOI: 10.1002/eji.1830271021. View

Lee C, Kondo S, Honjo T . Frequent but biased class switch recombination in the S mu flanking regions. Curr Biol. 1998; 8(4):227-30. DOI: 10.1016/s0960-9822(98)70087-9. View

Casellas R, Nussenzweig A, Wuerffel R, Pelanda R, Reichlin A, Suh H . Ku80 is required for immunoglobulin isotype switching. EMBO J. 1998; 17(8):2404-11. PMC: 1170583. DOI: 10.1093/emboj/17.8.2404. View

Manis J, Gu Y, Lansford R, Sonoda E, Ferrini R, Davidson L . Ku70 is required for late B cell development and immunoglobulin heavy chain class switching. J Exp Med. 1998; 187(12):2081-9. PMC: 2212369. DOI: 10.1084/jem.187.12.2081. View

10.

Bottaro A, Young F, Chen J, Serwe M, Sablitzky F, Alt F . Deletion of the IgH intronic enhancer and associated matrix-attachment regions decreases, but does not abolish, class switching at the mu locus. Int Immunol. 1998; 10(6):799-806. DOI: 10.1093/intimm/10.6.799. View

11.

Ballantyne J, Henry D, Muller J, Briere F, Snapper C, Kehry M . Efficient recombination of a switch substrate retrovector in CD40-activated B lymphocytes: implications for the control of CH gene switch recombination. J Immunol. 1998; 161(3):1336-47. View

12.

Hein K, Lorenz M, Siebenkotten G, Petry K, Christine R, Radbruch A . Processing of switch transcripts is required for targeting of antibody class switch recombination. J Exp Med. 1998; 188(12):2369-74. PMC: 2212419. DOI: 10.1084/jem.188.12.2369. View

13.

Dempsey L, Sun H, Hanakahi L, Maizels N . G4 DNA binding by LR1 and its subunits, nucleolin and hnRNP D, A role for G-G pairing in immunoglobulin switch recombination. J Biol Chem. 1999; 274(2):1066-71. DOI: 10.1074/jbc.274.2.1066. View

14.

Kinoshita K, Tashiro J, Tomita S, Lee C, Honjo T . Target specificity of immunoglobulin class switch recombination is not determined by nucleotide sequences of S regions. Immunity. 1999; 9(6):849-58. DOI: 10.1016/s1074-7613(00)80650-0. View

15.

Petry K, Siebenkotten G, Christine R, Hein K, Radbruch A . An extrachromosomal switch recombination substrate reveals kinetics and substrate requirements of switch recombination in primary murine B cells. Int Immunol. 1999; 11(5):753-63. DOI: 10.1093/intimm/11.5.753. View

16.

Ehrenstein M, Neuberger M . Deficiency in Msh2 affects the efficiency and local sequence specificity of immunoglobulin class-switch recombination: parallels with somatic hypermutation. EMBO J. 1999; 18(12):3484-90. PMC: 1171427. DOI: 10.1093/emboj/18.12.3484. View

17.

Schrader C, Edelmann W, Kucherlapati R, Stavnezer J . Reduced isotype switching in splenic B cells from mice deficient in mismatch repair enzymes. J Exp Med. 1999; 190(3):323-30. PMC: 2195591. DOI: 10.1084/jem.190.3.323. View

18.

Stavnezer J, Bradley S, Rousseau N, Pearson T, Shanmugam A, Waite D . 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 Immunol. 1999; 163(4):2028-40. View

19.

Lorenz M, Jung S, Radbruch A . Switch transcripts in immunoglobulin class switching. Science. 1995; 267(5205):1825-8. DOI: 10.1126/science.7892607. View

20.

Mowatt M, Dunnick W . DNA sequence of the murine gamma 1 switch segment reveals novel structural elements. J Immunol. 1986; 136(7):2674-83. View