The Dynamic Nature of the Antibody Repertoire

Antibody production by an animal in response to an immunogen is dictated by the repertoire of B cells at the time of stimulation. The repertoire of B cells, however, is continuously changing. This change is brought about by the dynamic character of the repertoire, and by the antigenic experience of the animal. The naive repertoire is formed by genetic recombination events which are independent of antigenic stimulation. Since the size of the B-cell repertoire only allows the expression of a fraction of the genetic repertoire at any given time, only a random sample of the total potential is available. This constitutes the raw material that must be capable of providing initial recognition to any antigenic challenge to which animals are subjected. This raises the question of how an animal discriminates between self and non-self antigens, an aspect of the response we will not discuss here. We want to restrict ourselves to points in which our experience of the anti-oxazolone response gives informative data. We will therefore concentrate our attention on describing the way in which the antigenic experience influences the available B-cell repertoire. Our general ideas on the subject will be discussed in the context of the model presented in Fig. 1. We will argue that antigensensitive B cells from both the naive and the memory repertoire are modified through hypermutation and selection following each round of antigenic stimulation, so as to continuously refme the pool of memory B cells. One of the important conclusions we draw from otir experiments is that the antigetiic stimulation of memory cells leads to further processes of hypermutation and selection, functioning through a highly organized and purpose-developed procedure, probably operating in the germinal centers (see Fig. 1). We wish to argue that the development of such an elaborate procedure, so far unique to antibody-producing B cells, arose in response to the evolutionary advantage