B cell repertoire ontogeny: heritable but dissimilar development of parental and F1 repertoires

This study examines the genetics of antibody repertoire ontogeny by the comparison of the repertoires in B10.D2, BALB/c, and (BALB X B10.D2)F1 mice at 12 to 14 days of age. This was accomplished by fine specificity analysis of clonotypes responsive to the influenza virus hemagglutinin in each strain. The results indicate that: a) neonatal antibody repertoires are in general less heterogeneous than their adult counterparts, which confirms and extends previous observations and reinforces the assertion that repertoire ontogeny is a heritable, patterned process; b) the BALB/c and B10.D2 neonatal repertoires differ from one another in clonotype compositions, facilitating genetic analyses of repertoire establishment; c) the BALB/c X B10.D2)F1 neonatal repertoire, although of restricted heterogeneity, is clearly dissimilar from either parental repertoire. These findings indicate that B cell repertoire ontogeny may be governed by heritable factors that interact with but are not necessarily themselves variable region structural genes. Furthermore, it appears that the expressed responsive B cell repertoire is a selected subset of the inherited potential repertoire.