THE HUMAN-IMMUNOGLOBULIN ALEPH LOCUS - CHARACTERIZATION OF THE DUPLICATED A-REGIONS

The central regions of the kappa-locus, the so-called A regions, have been fully characterized on cosmid and phage lambda-clones. The regions, which are parts of the C(kappa)-proximal and -distal copies of the locus and are, therefore, called Ap and Ad regions, comprise about 140 kb each and contain together 30 V(kappa) genes and pseudogenes. The A regions have been linked on their 5' sides to the O regions and on their 3' sides to the L regions. Chromosomal walking has eliminated a previous gap in the Ap region. Detailed restriction maps of the Ap and Ad regions and the sequences of 9 V(kappa) genes are reported. Four events, which have occurred in evolution probably after the duplication of the A region, were identified: the insertion of an Alu element in Ad; the insertion of part of a LINE element in Ap; the deletion of a 17.5-kb fragment including one V(kappa) gene from Ap; the sequence divergence of duplicated V(kappa) gene regions which ranges among the five pairs studied here from 0 to 14 bp per kb and converted two genes to pseudogenes while their duplicates stayed functional. An analysis of the A regions of the lymphoid cell lines RPMI 6140 and GM607 confirmed the previous finding that the V(kappa)-J(kappa) rearrangement in these cell lines had occurred by deletion and inversion mechanisms. respectively. Thus, the structural data contribute to the understanding of the evolution and the functioning of the A regions of the kappa-locus.