Class switch sequences

Yasui, H., Akahori, Y., Hirano, M., et al. (1989). Class switch from m to d is mediated by homologous recombination between sm and Sm sequences in human immunoglobulin gene loci. Eur. J. Immunol., 19, 1399-1403. 

To get an idea of the relative numbers of different types of dynamic behaviors, we have carried out simulation of randomly selected networks with fi = 1. Out of the 11223994 structural equivalence classes in four dimensions, about 8 out of 1000 networks have stable limit cycles, while about 1 out of 1500 appear to be chaotic. The others go to stable foci or stable nodes. Amongst the periodic networks, a few have very long periods and complex switching sequences as discussed above in Section V. B. Thus, surprisingly complex but nevertheless periodic switching behavior is possible. 

Class switch recombination is also found to take place in plasmacytoma and hy-bridoma cells. These rare variant cells can be detected in many cell lines at frequencies of 1(T4 to 1CT7 (see Section 2.2.5.). In all cases analysed so far intermediate CH genes have been deleted from the active IgH loci. Frequently, however, the recombination sites were outside of the switch region - most drastically in the IgD variants (see review [C]), there being no switch sequence in front of C5 [56], This could be the reason why in normal B cells switching from IgM to IgD is rare upon activation. 

The conservation of repetitive elements in S regions has led to the working hypothesis that such elements play a central role in the switch rearrangement. About 20 DNA sequences of the recombination junctions of various class-switches have been determined in order to get information on the sequence requirements of switch recombination [63-80,83,85], Comparison of these sequences makes it clear that the enzymes involved in class-switching do not recognize an obviously well conserved sequence. 

It would seem from the present findings that the specificity of class-switch recombination is not mediated by consensus sequences in the S regions. It is more likely that the control of class-switching operates at the level of chromatin structure which may be influenced by repetitive sequences. 

Figure 6 Immunoglobulin heavy chain class switch recombination. (A) The murine heavy chain locus is shown before and after recombination from g. to yl, which results in expression of IgGl antibodies. Deleted sequences can be recovered in circular DNA molecules from B cells which have recently completed switch recombination. V, variable region C, constant region and S, switch region. (B) Examples of consensus G-rich repeats from some murine S regions...

Ehrenstein, M. R., and Neuberger, M. S. (1999). Deficiency in msh2 affects the efficiency and local sequence specificity of immunoglobulin class-switch recombination parallels with somatic hypermutation. EMBO J. 18, 3484—3490. 

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