ONTOGENY OF THE HEAVY-CHAIN IMMUNOGLOBULIN REPERTOIRE IN FETAL LIVER AND BONE-MARROW

We studied the kinetics of maturation of B cell progenitors in the mou se embryo, from day 15 of development to birth, both in liver and bone marrow. The analysis of Ig heavy chain rearrangements at different ti me points of late fetal development shows that oligoclonal patterns of V-H-D-J(H) rearrangements are detected by day 15 in fetal liver. The pattern is polyclonal and diverse by day 17; however, 80% of the rearr angements are nonproductive. In bone marrow, the pattern of rearrangem ents is less diverse at birth, although the percentage of nonproductiv e rearrangements approaches adult bone marrow levels (35-40%). After d ay 17 in fetal liver, there is a sudden reversal in the percentage of nonproductive rearrangements that reaches 33% at day 19 (birth), Matur ation of B cells, as measured by the fraction of surface Ig(+) in tota l B220(+) cells and the presence of N sequence additions in V-H-D-J(H) joints, occurs in the marrow before fetal liver. These results demons trate that the lymphopoietic environment in fetal liver and bone marro w of animals at the same stage of development is functionally distinct .