CONSTITUTIVE EXPRESSION OF TERMINAL DEOXYNUCLEOTIDYL TRANSFERASE IN TRANSGENIC MICE IS SUFFICIENT FOR N-REGION DIVERSITY TO OCCUR AT ANY IGLOCUS THROUGHOUT B-CELL DIFFERENTIATION

N region diversity in Ag receptors is a developmentally regulated proc ess in B and T cells that correlates with the differential expression of terminal deoxynucleotidyl transferase (TdT), Absent in fetal and ne wborn mice, TdT expression is restricted to early T and pro-B cells in adults. To extend the TdT expression pattern throughout B cell ontoge nesis, we generated transgenic mice carrying a TdT cDNA under the regu latory elements of the N-myc gene and the IgH enhancer, High expressio n was observed in secondary lymphoid organs consistent with TdT activi ty beyond the pre-B cell stage, This suggests that TdT transgene expre ssion is not down-regulated as is the endogenous gene. Unlike normal m ice, extensive N region diversity was found in rearranged lambda light chain genes of adult transgenic animals. Therefore, expression of TdT appears sufficient for N region diversity to occur at any Ig locus. M ore importantly, expression of the transgene takes place during fetal development. As a consequence, the potential fetal B cell repertoire i s modified as both rearranged heavy and light chain genes now show N r egion additions, Constitutive expression of TdT throughout B cell diff erentiation does not therefore appear deleterious and suggests that Td T is recruited only to participate in the V(D)J recombination process.