ABSTRACT
Although it often seems that we understand the basic mechanisms and processes generating a diverse antibody repertoire, it should not be a surprise that what appears to have been solved, on closer inspection, retains multiple enigmatic features. To be sure, our increased knowledge has been accompanied by changes in the framing of the questions and the depth of insight that we now desire. In our laboratory we have had a longstanding interest in forging a meaningful understanding of the relationship between the inherited set of V gene segments and the actual utilization of these V gene segments by B cells. The questions abounded. How many VH gene segments were there? Could we define them and know each one personally? How were they organized in the locus? How polymorphic were the VH genes? Was the V gene disease hypothesis tenable? What was the basis for restricted VH expression in the fetal repertoire? How did the fetal repertoire differ from the adult repertoire? Of which genes and in what proportion was the adult repertoire comprised?
