Patterned acquisition of the antibody repertoire: diversity of the hemagglutinin-specific B-cell repertoire in neonatal BALB/c mice

Abstract

The B-cell response of 12- to 14-day old BALB/c mice to the hemagglutinin molecule of influenzae virus A/PR/8/34(H0N1) has been examined with monoclonal antibodies obtained by the splenic focus technique. An analysis of the specificity of these antibodies with a panel of heterologous viruses indicates that the antibody repertoire is highly restricted at an intermediate stage in postnatal development of the immune system. In toto, only 10 distinct reactivity patterns have been observed in an analysis of 72 antibodies derived from 28 donors. This contrasts with a substantially more diverse repertoire present in nonimmune and immune adult populations. The neonatal antibody specificities do not appear to be a random sampling of adult specificities, because several clonotypes (as defined by reactivity pattern) frequently found in neonates are rare or absent in adults. Most importantly, the vast majority of adult clonotypes are absent from the neonatal repertoire. These findings indicate that, at a developmental stage when the B-cell repertoire contains at least 10(6) clonotypes, the repertoire of genetically identical individuals is shared. This is consistent with a diversification process that is highly patterned and genetically determined. Furthermore, because 12- to 14-day-old neonates exhibit a diversified but definable hemagglutinin-specific B-cell repertoire, this experimental system should enable precise analyses of genetic and environmental influences on repertoire expression.