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 (V_H ), diversity (D_H ), and junctional (J_H ) 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 V_H locus has been completely delineated. This cluster comprises 6 functional J_H genes, more than 30 D_H segments, and approx 100 nonallelic V_H genes that have been categorized in at least 7 families. V_H 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 V_H families vary in size ranging from one member in the V_H 6 family to over 30 in the V_H 3 family (2 ).