Dynamics of B cell repertoire formation: normal patterns of clonal turnover are altered by ligand interaction

The dynamics of B cell repertoire formation was examined by defining the kinetics and clonal composition of the influenza hemagglutinin- (HA) responsive BALB/c repertoire at 1 and 2 wk of age. Although the size and diversity of the HA-responsive repertoire remain constant during this period, the clonal composition changes significantly. These findings indicate a rapid and regular turnover of clonal specificities within the emerging primary repertoire. In addition, the effect of ligand exposure on this process was analyzed by characterizing the repertoire of 2-wk-old BALB/c mice that had been immunized with virus during their first week of life. This treatment markedly alters the normal kinetics and turnover of the emerging repertoire. First, many clonotypes that normally arise between 1 and 2 wk of age fail to be expressed in detectable numbers. Second, several clonotypes that are normally only transiently expressed at 1 wk of age are preferentially expanded and preserved within the responsive B cell pool. In conjunction, these results demonstrate that a) the primary repertoire is characterized by rapid and regular turnover in clonotype composition, b) antigenic exposure perturbs the normal kinetics and pattern of this turnover, and c) the exact effects of ligand exposure may depend on the developmental stage at which it occurs.