2 BCR or NOT 2 BCR – Receptor dilution: a unique mechanism for preventing the development of holes in the protective B cell repertoire

Abstract

The clonal selection theory and the associated corollaries have had a major influence in shaping our thinking about lymphoid cell development as well as how these cells respond to antigenic challenges. Among these concepts are that a single B cell expresses a single receptor with a single antigen specificity. While these hypotheses have proven invaluable in expanding our understanding of immune response, over time numerous observations have been made that suggest that the single cell, single receptor, single specificity model is not absolute. In this manuscript, we review this literature as it pertains to B cells and provide a summary that supports the notion that in certain situations, the overarching rules by which we consider development and response of immune cells may be compromised. The result of compromising allelic and isotype exclusion is a small but real population of dual receptor expressing B cells. A number of mechanisms that have been proposed for generating these dual expressing B cells are presented and discussed. We also consider the negative implications of dual receptor expression on regulating and controlling autoreactive B cell populations as well as its beneficial contributions to preserving essential receptor specificities and thereby preventing the development of holes in the immune repertoire. Previously, the dual receptor expressing population has received relatively little attention. Improvements in the tools available to examine individual B cell populations have resulted in our identification of and discrimination between novel populations of B cells, including novel dual receptor expressing populations. This combined with continuing increases in our understanding of how the immune repertoire relates to a protective immune response will strengthen and further define this novel aspect of immune cell development.