Alternative routes to maturity: branch points and pathways for generating follicular and marginal zone B cells

Positive and negative selection of developing B cells is critical for generating a functional non-pathogenic B-cell repertoire. Newly formed B cells in the bone marrow or peripheral lymphoid system can be eliminated by one of several negative selection mechanisms or recruited through a poorly understood positive selection mechanism. In this review, we focus on the growing literature on the relevance of immature (transitional) peripheral B cells to the area of B-cell positive selection, with an emphasis on the notion that transitional B cells can be subdivided into several functionally distinct subpopulations. In this discussion, we consider the nature of these transitional B-cell subsets and their relevance to selection events that influence whether developing B cells eventually give rise to follicular versus marginal zone B cells. In addition, we attempt to initiate a resolution of current controversies surrounding transitional B-cell subsets and offer an alternative model of peripheral B-cell maturation and the follicular versus marginal zone decision.