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

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Abstract
Summary:  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.