Genetic diversity of the human immunoglobulin heavy chain VH region

The human immunoglobulin heavy chain V-H region is one of the most complex regions in the human genome. The high level of diversity of this region has been shown by a number of studies. However, because of the limitations of the conventional experimental methods, it has been difficult to learn the extent of the diversity and the underlying mechanisms. This review describes a number of new genetic approaches developed in the authors' laboratory. By using these approaches, significant progress has been made in assigning different V-H sequences to their respective loci, in learning the diversity of gene segment number and composition among the V-H haplotypes, and in learning V-H gene segment organization in individual haplotypes. Information obtained toward this direction could help in understanding the mechanisms underlying V-H region diversity and the biological impact of the V-H region diversity.