Comparative expression of adult and fetal V gene repertoires

Abstract

A hallmark of the immune system is the extraordinary diversity associated with antibodies. This is made possible by a series of genetic rearrangements involving variable region gene segments. Considerable detail is known about these genetic mechanisms except for the enzymatic machinery involved. An important question in studies of the generation of diversity is whether V genes are selected for rearrangement mainly in a random manner or selected by particular developmental rules. Past studies have indicated that the acquisition of fetal and neonatal specificity repertoires is a nonrandom process. In this report, we review our studies that directly compare the adult and fetal/neonatal V gene repertoires. The evidence suggests that the adult repertoire is more diverse with indications of a random use of VH gene families. However, whether V genes are indeed randomly used in the adult remains to be clarified at the VH gene member level. The fetal repertoire, on the other hand, appears nonrandom in V gene usage. In addition, the fetal repertoire is mostly germline encoded with little evidence of junctional diversity. Taken together, the results indicate different rules for generation of the adult and fetal repertoires, findings most likely explain by distinct B cell subsets and B cell progenitors at early stages in ontogeny.