BIASED UTILIZATION OF D-HQ52 AND J(H)4 GENE SEGMENTS IN A HUMAN IG TRANSGENIC MINILOCUS IS INDEPENDENT OF ANTIGENIC SELECTION

We have assessed the effect of antigenic selection on human Ig heavy c hain D and J(H) gene segment utilization in mice that contain transgen es composed of 2 V-H (psi V(H)3-105 and V(H)5-251), 10 D, 6 J(H), C mu , andsegments. Human heavy chains using the functional V(H)5-251 gene segment are expressed in the serum and on the surface of murine B cell s. The second V-H gene segment (psi V(H)3-105) is not expressed as a p rotein but is rearranged and transcribed into mRNA. We previously repo rted that the functional V(H)5-251 mu transcripts preferentially used the D-HQ52 and J(H)4 gene segments similar to their use in the human r epertoire. Here, we demonstrate that the nonfunctional (psi V(H)3-105) gene segment shows the same bias in D and J(H) segment utilization. B ecause transcripts using the pseudo-V-H gene subjected to antigenic se lection, we conclude that the restricted repertoire observed is Ag ind ependent. Analysis of pseudo V-H gene segment recombination products r eveals no bias in D gene segment reading frame utilization. Finally, w e demonstrate that in the human transgene coding sequence complementar ities can affect the recombination site and the D inversion is common.