Class-switch recombination mechanism

Yu, K., and Lieber, M. (2003). Nucleic acid structures and enzymes in the immunoglobulin class switch recombination mechanism. DNA Repair 1163-1174. 

C. H., and Alt, F.W., Mechanism and control of V(D)J recombination versus class switch recombination similarities and differences, Adv. Immunol. 86, 43-112, 2005 Aplon, P.D., Causes of oncogeific chromosomal translocation. Trends Genet. 22, 46-55, 2006. 

In polyclonally activated B cells class switch recombination precedes or rapidly follows the switch in CH-gene expression. Switching by a differential RNA splicing mechanism would apply for a very short period, if at all. The frequency of cells expressing surface IgG3 begins to increase after day 3 of LPS stimulation and already by day 6 about half of the IgH loci of these cells have performed switch recombination. 

Ehrenstein, M. R., Rada, C., Jones, A. M., Milstein, C., and Neuberger, M. S. (2001). Switch junction sequences in PMS2-deficient mice reveal a microhomology-mediated mechanism of Ig class switch recombination. Proc. Natl. Acad. Set. USA 98, 14553-14558. 

Honjo, T., Kinoshita, K., and Muramatsu, M. (2002). Molecular mechanism of class switch recombination Linkage with somatic hypermutation. Annu. Rev. Immunol. 20, 165-196. 

Seising E Ig class switching targeting the recombinational mechanism. Curr Opin Immnol 2006 18 249-254. 

The differences in the structures of the various switch regions raise the possibility of class-specific switch recombination, which would make no sense without a corresponding regulatory mechanism. It is known that the frequency of cells expressing various immunoglobulin classes can be regulated by T cell derived lym-phokines [3-9], although no lymphokine has been clearly demonstrated to induce the switch directly rather than to expand switched cells or switch precursors. 

---