V(D)J rekombinacija

V(D)J rekombinacija (somatska rekombinacija) je mehanizam genetičke rekombinacije u ranim stupljevima imunoglobulinske (Ig) i TCR produkcije imunskog sistema. V(D)J rekombinacija se odvija u primarnim limfoidnim tkivima (koštanoj srži za B ćelije, i u grudnoj žlezdi za T ćelije). V(D)J rekombinacija skoro randomno kombinuje varijabilne, raznovrsne i spajajuće (engl. Variable, Diverse, and Joining) genske segmente kičmenjaka, i zbog slučajnosti u izboru različitih gena je u stanju da kodira raznovrsne proteine koji odgovaraju antigenima sa bakterija, virusa, parazita, disfunkcionalnih ćelija kao što su ćelije tumora,[1] i polena.

Molekuli ljudskih antitela (i B ćelijski receptori) sastoje se od teških i lakih lanaca sa konstantnim (C) i varijablnim (V) regionima koji kodiraju gene tri lokusa.

  1. Imunoglobulinski teški lokus (IGH@) na hromozomu 14, koji sadrži gene za imunoglobulinski teški lanac
  2. Imunoglobulinski kapa lokus (IGK@) na hromozomu 2, koji sadrži gene za imunoglobulinski laki lanac
  3. Imunoglobulinski lambda lokus (IGL@) na hromozomu 22, koji sadrži gene za immunoglobulin laki lanac

Višestruki geni za varijabilne regione su kodirani u ljudskom genomu koji sadrži tri distinktna tipa segmenata. Na primer, region imunoglobulinskog teškog lanaca sadrži 44 varijabilna (V) gena[2] plus 27 D gena i 6 J gena.[3] Laki lanci takođe poseduju brojne V i J gene, ali nemaju D gene. Mehanizmom DNK preuređivanja tih regionalnih gena moguće je generisati enormni repertoar antitela; oko 3×1011 kombinacija je moguće, mada se neke uklanjaju zbog samoreaktivnosti.

Reference

  1. ↑ Abbas AK and Lichtman AH (2003). Cellular and Molecular Immunology (5th izd.). Saunders, Philadelphia. ISBN 0-7216-0008-5. 
  2. ↑ Matsuda, F; Ishii, K; Bourvagnet, P; Kuma, K; Hayashida, H; Miyata, T; Honjo, T (1998). „The complete nucleotide sequence of the human immunoglobulin heavy chain variable region locus”. The Journal of experimental medicine 188 (11): 2151–62. PMC 2212390. PMID 9841928. 
  3. ↑ Li A, Rue M, Zhou J et al. (June 2004). „Utilization of Ig heavy chain variable, diversity, and joining gene segments in children with B-lineage acute lymphoblastic leukemia: implications for the mechanisms of VDJ recombination and for pathogenesis”. Blood 103 (12): 4602–9. DOI:10.1182/blood-2003-11-3857. PMID 15010366. 

Literatura

  • Hartwell LH, Hood L, Goldberg ML, Reynolds AE, Silver LM, Veres RC (2000). Chapter 24, Evolution at the molecular level. In: Genetics. New York: McGraw-Hill. str. 805–807. ISBN 0-07-299587-4. 
  • V(D)J Recombination. Series: Advances in Experimental Medicine and Biology, Vol. 650 Ferrier, Pierre (Ed.) Landes Bioscience 2009, XII, 199 p. ISBN 978-1-4419-0295-5.
  • Abbas AK and Lichtman AH (2003). Cellular and Molecular Immunology (5th izd.). Saunders, Philadelphia. ISBN 0-7216-0008-5. 

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