IMMUNOGLOBULIN D-H RECOMBINATION SIGNAL SEQUENCE TARGETING - EFFECT OF D-H CODING AND FLANKING REGIONS AND RECOMBINATION PARTNER

V(D)J recombination is targeted by recombination signal sequences (RSS ) located immediately adjacent to immune receptor gene segments, While the RSS flanking D-H segments appear to be equivalent, they are not r andomly utilized. During D-H to J(H) rearrangement, the 3' D-H RSS is virtually exclusively utilized, suggesting that the 3' D-H RSS could s imply be a better target for the recombinase, However, when we examine d V-H to D-H (without J(H)) rearrangements, we found that the preferen ce for D-H RSS use changes, so that the 5' D-H RSS are preferred, This suggests that the 3' D-H RSS are not simply superior targets for the V(D)J recombinase, but instead that certain 12/23-bp spacer RSS combin ations work better together to target recombination than do others, We have analyzed a series of artificial recombination substrates to deli neate cis sequences that affect D-H RSS selection, Our data suggest th at coding sequences adjacent to the D-H RSS, flanking sequences outsid e the D-H gene segment itself, and recombination partner all affect D- H RSS targeting.