Rearrangements at the light chain loci

The assembly of k variable regions seems to involve an inversion joining mechanism (see Section 2.2.). It is, therefore, likely that many or all mouse VK segments have an inverted orientation relative to the JK cluster and it is even possible that VK segments are not situated 5 but 3 to the JK locus on mouse chromosome 6. A detailed study of rearranged JK alleles in B cells actually demonstrated that both inversions and deletions frequently occur during assembly of k variable re- 

The A locus of the mouse carries only two VA segments but four CA exons which are organized in two clusters (CA3-CA1 and CA2-CA4) ([90,91], for a review see [92]). A single JA segment is found 1.3 kb 5 of each CA exon. The location and orientation of the VA segments with respect to the two CA clusters is presently unknown. However, because VA1 is in most cases appended to JA1 or JA3 while VA2 is connected to JA2, it is assumed that VA1 lies 5 of the CA1 cluster and VA2 lies 5 of the CA2 cluster [92]. In rare cases, a VA2 to JA3 or JA1 joint was found [93], The existence of these joints suggested that the Va2-Ca2 cluster lies 5 of the VA1-CA cluster. In the mouse, only 5% of all immunoglobulin-positive B cells ex- 

Because a single VA1 segment is present on each allele, mouse B cells have only two chances to generate a productive A1 light chain this happens with a one in three chance on each allele. However, a sequence analysis of productive VA1 genes revealed that several of them may have been derived from non-functional (out of phase) VA1JA1 complexes by an, as yet unknown, mechanism deleting one or two nucleotides close to the VA-JA joint [95]. 

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