Regulation of Gene Rearrangement

Early evidence pointing to a restriction in immunoglobulin expression was the demonstration that, in individuals who are heterozygous for allotype, myeloma proteins carry one or the other, but never both, of the allelic determinants found in the pooled immunoglobulin of that person (M rtensson, 1961 Harboe et al., 1962). This finding was interpreted to indicate that the alternate allotypic determinants are present on different immunoglobulin molecules, which are produced by different cells. Oudin (1960) had observed a presumably related phenomenon in rabbits. 

In 1963, shortly after the four-chain model for immunoglobulins was proposed, Dray and Nisonoff showed that immunoglobulin molecules from rabbits heterozygous for allotypic determinants at a light chain locus contain either light chains of one allotype, or of the other, but not both. These authors did not interpret the results 

A consequence of a strict stochastic model is that not all B lymphocytes will exhibit allelic exclusion. If the rate of productive rearrangement is sufficiently high, there will be occasional double producers (see related discussion in Part I, Instruction and Selection). On the other hand, if the rate of productive rearrangement is low, there will be few doubles, but many cells will have only non-functional rearrangements. 

A similar proposal was subsequently advanced for heavy chain rearrangements (Altet al., 1981) synthesis of a functional heavy chain in someway signals the cell to cease further V(D)J rearrangement. An alternate explanation for the presence in a B cell of no more than one heavy chain, proposed by Wabl and Steinberg (1982), 

The involvement of the pre-B cell receptor in allelic exclusion at the heavy chain locus is reminiscent of the original suggestion of Alt et al. (1980a) that surface IgM 

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