Cell lineage relationships were examined in large numbers of hybridomas derived from a single mouse at 7 days and from a single mouse at 12 days after a primary immunization. The properties of these developing lineages provide unique insight into their biologic selection and differentiation. The unique VDJ junctions, the characteristics of the somatic mutations, and the nonproductive H chain gene rearrangements observed at day 12 all indicate that the hybridomas were derived from a limited number of progenitor B cells. Clonally related hybridomas were also observed at day 7. The activation of these lineages occurred very early, because somatic variants were strongly selected for within a few days after the primary immunization.