Comparison of junctional diversity in the neonatal and adult immunoglobulin repertoires

Abstract

Junctional diversity in immunoglobulin (Ig) from an adult mouse contributes significantly to the size of the final Ig repertoire. In adult pre-B cells, N region addition and deletion of nucleotides form coding regions produces very heterogenous CDR3 sequences. In contrast, Ig from fetal and newborn mice show very restricted junctional diversity. The reasons for this are: (a) the lack of N regions; and (b) the predominance of certain junctional sequences. These common junctional sequences all appear to occur by targeted rearrangement to short stretches of sequence homology near the ends of the segments to be joined. Targeted rearrangement may play a role in the overexpression of certain Vh genes early in ontogeny. These non-random junctional sequences in the neonate will reproducibly create certain Ig, for example, the dominant T15 anti-PC antibodies. Thus the immune system first creates a small repertoire of predictable Ig sequences. To the extent that these Ig are expressed in long-lived B cells, these early Ig sequences may persist in the adult. Superimposed upon this early repertoire is an enormously diverse adult Ig repertoire.