Pairing of Variable Heavy and Variable κ Chains in Individual Naive and Memory B Cells

Abstract

A functional Ig consists of two heterodimers each of which is composed of a heavy and a light chain. Although there is increasing knowledge about the events that govern the rearrangement of the genes encoding each individual chain, only very limited information is available about the mechanisms governing the pairing of variable heavy (VH) and variable light (VL) chains. Using a single cell PCR, we were able to obtain VH and Vκ chains from 144 individual human CD19+/IgM+ B cells. Pairing of specific VH or Vκ families was not observed, nor was the length or the amino acid composition of the CDR3s of VH and Vκ chains in individual B cells similar. Comparison of VH and Vκ genes in B cells in which one or both contained evidence of somatic hypermutation with those with no mutations revealed a significant decrease in the mean length of the VH CDR3. Moreover, there was a significant correlation between the frequencies of mutations in VH and Vκ gene pairs in individual B cells. These results indicate that Ag-mediated selection as opposed to VHDJH recombination or subsequent Ig chain pairing tended to approximate the CDR3 lengths and the frequency of mutations of VH and Vκ in individual B cells.