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Human Immunoglobulin Heavy-Chain Variable Region Genes: Organization, Polymorphism, and Expression

1991; Elsevier BV; Linguagem: Inglês

10.1016/s0065-2776(08)60774-9

1557-8445

Virginia Pascual, J. Donald Capra,

T-cell and B-cell Immunology

The division of human immunoglobulin genes into various families was initially obvious from the protein data, although it appears that significant portions of the repertoire were missed by sequencing myeloma proteins. The reasons for this still remain clouded. However, using molecular techniques, most of the gene families have now been uncovered and their numbers, location, etc. are slowly being sorted out. A major surprise has been the significant interdigitation of the human VH genes, considering the clustering of similar VH genes in the mouse. Polymorphism has always been a hallmark of the immune system, and some of the earliest insights into the genetics of immunoglobulins were deduced from examinations of the polymorphisms of the constant region of human IgG. Polymorphism in the variable regions was expected and was initially thought to be an explanation for distinctions in immune responses among different individuals. To some extent, VH polymorphism was thought to be relevant to the notion of shared idiotypic specificities among antibodies with similar specificities in the human population. At the organizational level, it remains striking that over half of the gene segments in the VHI and VHIII families appear to be pseudogenes, whereas the VHIV, VHV, and VHVI families contain so few. Too little is known about the VHII family to draw inference in this regard. The forces that lead to diversification and selection in the somatic cells are likely to be similar to those that lead to preservation of specific VH genes in the germ cells.