Rendón-Anaya M, Alagón A

Language: Spanish
References: 16
Page: 19-29
PDF size: 171.09 Kb.

ABSTRACT

The immune system is capable of specifically recognizing an immense variety of antigens, due to the presence of receptors which are encoded by a very limited number of functional germline exons. Therefore, the B lymphocytes use four mechanisms of somatic antibody diversification that modify the sequence of the immunoglobulin genes, in order to optimize the specificity of the antigen receptors. These mechanisms involve different genomic and enzymatic factors, which broadly belong to DNA repair pathways. Thus, studying the molecular basis of the antibody diversification has been a very important source of immunological knowledge, and has improved our understanding regarding the pathways which maintain genomic integrity.

REFERENCES

1. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002) Molecular Biology of the Cell. Garland Science, New York, NY, USA, p 1375-1384.

2. Maizels N (2005) Immunoglobulin gene diversification. Annu Rev Genet 39: 23-46.

3. Ramón-Maiques S, Kuo AJ, Carney D, Matthews AGW, Oettinger MA, Gozani O, Yang W (2007) The plant homeodomain finger of RAG2 recognizes histone H3 methylated at both lysine-4 and arginine-2. PNAS 104: 18993-18998.

4. Corneo B, Wendland RL, Deriano L, Cui X, Klein IA, Wong SY, Arnal S, Holub AJ, Weller GR, Pancake BA, Shah S, Brandt VL, Meek K, Roth DB (2007) Rag mutations reveal robust alternative end joining. Nature 449: 483-487.

5. Petersen-Mahrt SK, Harris RS, Neuberger MS (2002) AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification. Nature 418: 99-103.

6. Arakawa H, Saribasak H, Buerstedde JM (2004) Activation-induced cytidine deaminase initiates immunoglobulin gene conversion and hypermutation by a common intermediate. PLoS Biol 2: 967-974.

7. Shinkura R, Ito S, Begur NA, Nagaoka H, Muramatsu M, Kinoshita K, Sakakibara Y, Hijikata H, Honjo T (2004) Separate domains of AID are required for somatic hypermutation and class-switch recombination. Nat Immunol 5: 707-712.

8. Teng G, Papavasiliou FN (2007) Immunoglobulin somatic hypermutation. Annu Rev Genet 41:107-120.

9. Di Noia JM, Neuberger MS (2007) Molecular mechanisms of antibody somatic hypermutation. Annu Rev Biochem 76: 1-22.

10. Yang SY, Fugmann SD, Schatz DG (2006) Control of gene conversion and somatic hypermutation by immunoglobulin promoter and enhancer sequences. J Exp Med 203: 2919-2928.

11. Sale JE (2004) Immunoglobulin diversification in DT40: a model for vertebrate DNA damage tolerance. DNA Repair 3: 693-702.

12. Tang ES, Martin A (2007) Immunoglobulin gene conversion: synthesizing antibody diversification and DNA repair. DNA Repair 6: 1557-1571.

13. Cummings WJ, Munehisa Yabuki M, Ellen C. Ordinario EC, David W. Bednarski DW, Simon Quay S, Nancy Maizels N (2007) Chromatin structure regulates gene conversion. PLoS Biol 5: 2145-2155.

14. Wuerffel R, Wang L, Grigera F, Manis J, Selsing E, Perlot T, Alt FW, Cogne M, Pinaud E, Kenter AL (2007) S-S synapsis during class switch recombination is promoted by distantly located transcriptional elements and activation-induced deaminase. Immunity 27: 711-722.

15. Yan CT, Boboila C, Souza EK, Franco S, Hickernell TR, M, Gumaste S, Geyer M, Zarrin AA, Manis JP, Rajewsky K, Alt FW (2007) IgH class switching and translocations use a robust non-classical end-joining pathway. Nature 449: 478-483.

16. Wu X, Stavnezer J (2007) DNA polymerase beta is able to repair breaks in switch regions and plays an inhibitory role during immunoglobulin class switch recombination. J Exp Med 204: 1677-1689.