VHD rearrangements in human immunoglobulin heavy chain minilocus transgenic mice

Abstract

Typically, immunoglobulin VHDJH recombination is performed in two steps with D to JH rearrangement preceding VH to DJH rearrangement. Using a human immunoglobulin heavy chain transgenic minilocus, we previously demonstrated that a non‐conventional human D gene segment termed DIR2 could be recombined to a VH gene segment to form VHD rearrangements. Here, we demonstrate that VHD rearrangements involve conventional D gene segments as well. VHD rearrangements are easily detected and are diverse. Similarly to DJH rearrangements, VHD rearrangements occur by deletion and inversion. They occur approximately 1000 times less frequently than DJH rearrangements. VHD rearrangements can constitute intermediates for the formation of VHDDJH rearrangements.

Evidence That Terminal Deoxynucleotidyltransferase Expression Plays a Role in Ig Heavy Chain Gene Segment Utilization

“…1). Several mechanisms of recombination have been extensively studied in this system (27)(28)(29)(30)(31)(32). In this paper we analyze human IgH rearrangements generated at the DNA level in pHC1 minilocus transgenic mice, in the presence or absence of TdT.…”