Repertoire Diversification of Primary vs Memory B Cell Subsets

Abstract

The immune system accomplishes the specific recognition of foreign antigens, in the absence of reactivity to self antigens, by: (a) creating an enormous repertoire of cells each expressing an unique variable (V) region (clonotype); (b) purging the repertoire of cells whose V regions recognize self-antigenic determinants, and (c) enabling each immunogen to selectively stimulate only those cells whose V regions are high affinity for determinants of that immunogen. While this overall strategy is pervasive among both the B and T cell systems of immunocompetent animals, there is enormous variation in the extent of repertoire diversity and the means by which repertoire diversity is achieved, even among the B cell subsets of an individual. Thus, prior to any overt antigenic stimulation, the murine B cell system consists of at least four distinct B cell subsets differing in repertoire diversity and responsiveness to antigenic stimulation. After immunization, the repertoire is supplemented by the generation of memory B cells, which in some, but not all cases, enables the refinement of that portion of the repertoire that initially recognized the immunogen. The existence of a mechanism that improves the pre-existing repertoire suggests that the initial repertoire may have been functionally deficient in the spectrum of V regions capable of high affinity recognition of certain antigens. In this sense the generation of memory B cells can fill these gaps, the strategy for V region diversification used to generate and propagate memory B cells would appear to be both unique and extremely powerful.