Affinity Maturation of the Primary Response by V Gene Diversification

Abstract

A key feature of the primary immune response to T cell-dependent antigens is the increase in the average affinity of antigen-specific antibody during the course of the response (Eisen and Siskind 1964; Siskind and Benaceraff 1969). Indeed, the affinity of serum antibody for antigen in the late stages of the primary response is often equal to that of the secondary or memory response. The basis of high-affinity memory responses is well understood; V gene somatic hyper-mutation and B cell selection in the germinal center (GC) results in the generation of a population of recirculating memory B cells containing high affinity variants (Gray 1994; Rajewsky 1996). The basis of affinity maturation of primary response serum antibody, however, is much less well understood. While it is often assumed that the process is very similar, if not identical, to that of the generation of memory B cells, few details have been determined. This chapter describes recent results from our laboratory and others which address the issue of affinity maturation of antibody-secreting cells in the primary response using the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP) coupled to a protein carrier as a model system.