Detection of Human Variable Gene Family Expression at the Single-Cell Level

In mammals, the genes encoding the variable (V) domains of the immunoglobulin heavy (H) chain are assembled during lymphocyte development by rearrangements of variable (VH ), diversity (DH ), and junctional (JH ) gene segments (1 ). Selection of these gene elements from their corresponding libraries of germ-line genes is governed by a site-specific, developmentally ordered process. In humans, the organization of the VH locus has been completely delineated. This cluster comprises 6 functional JH genes, more than 30 DH segments, and approx 100 nonallelic VH genes that have been categorized in at least 7 families. VH gene members within a given family are highly homologous with >80% sequence identity, whereas the degree of homology between members of distinct families is usually <70%. Human VH families vary in size ranging from one member in the VH 6 family to over 30 in the VH 3 family (2 ).