title: Hematopoietic stem cell-independent B-1a lineage.
abstract: The accepted dogma has been that a single long-term hematopoietic stem cell (LT-HSC) can reconstitute all components of the immune system. However, our single-cell transfer studies have shown that highly purified LT-HSCs selectively fail to reconstitute B-1a cells in otherwise fully reconstituted hosts (i.e., LT-HSCs fully reconstitute follicular, marginal zone, and B-1b B cells, but not B-1a cells). These results suggest that B-1a cells are a separate B cell lineage that develops independently of classical LT-HSCs. We provide an evolutionary two-pathway development model (HSC independent versus HSC dependent), and suggest that this lineage separation is employed not only by B cells but by all hematopoietic lineages. Collectively, these findings challenge the current notion that LT-HSCs can reconstitute all components of the immune system and raise key questions about human HSC transplantation. We discuss the implications of these findings in light of our recent studies demonstrating the ability of B-1a cells to elicit antigen-specific responses that differ markedly from those mounted by follicular B cells. These findings have implications for vaccine development, in particular vaccines that may elicit the B-1a repertoire.
authors.affiliation: Department of Genetics and Immunology Program, Stanford University School of Medicine, Stanford, California.
authors.forename: Eliver Eid Bou
authors.initials: EE
authors.lastname: Ghosn
authors.affiliation: Department of Genetics and Immunology Program, Stanford University School of Medicine, Stanford, California.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation / Q000639:trends; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans
keywords: B cell development; HSC; hematopoiesis; transplantation; vaccine