Multiple waves of fetal‐derived immune cells constitute adult immune system

Abstract

The stem cell hypothesis is a central dogma in hematology and immunology that proposes that all blood cells are produced by hematopoietic stem cells (HSCs). An HSC is defined as a cell that has self-renewal and multilineage differentiation capacity, which can be proven only by transplantation assays. Numerous efforts to isolate HSCs from adult bone marrow (BM) at the single-cell level have been made, 1,2 and one HSC has been shown to repopulate blood cells of all five lineages (erythroid, megakaryocyte, myeloid, T-cell and B-cell lineages) following transplantation into lethally irradiated congenic recipient mice. 3 Precise observation of blood lineage engraftment patterns by single HSCs has revealed that the outputs of HSCs are different between HSCs of different ages and even after secondary transplantation, highlighting the heterogeneity of HSCs. 3,4 However, these studies did not always include donor-derived tissue-resident immune cells in their analysis, leaving the origins of some tissueresident immune cells unclarified.It is now recognized that some tissue-resident immune cells are fetal-derived and are not the progeny of adult HSCs. For example, Vγ3-T cells in the skin are produced only during the fetal period

Layered immune system development in mice and humans

“…10,11 The erythromyeloid progenitors (EMPs) that arise as early as E8.25 in the yolk sac also generate mast cells, some of which are maintained in the adult. The contributions from Kobayashi and Yoshimoto 12 and from Chia et al 13 address the origin of mast cell progenitors during this early wave of yolk sac hematopoiesis as well as at later stages of development. In addition to discussing the origins of mast cells in different waves of hematopoiesis, the comprehensive chapter from Chia et al reviews the impact of mast cells on various developmental and pathologic processes.…”

“…Many of these revelations were initially made by Momoko Yoshimoto in collaboration with Mervyn Yoder and subsequently in her own independent laboratory and are summarized in the review by Kobayashi and Yoshimoto. 12 The degree to which B and T cells derived from this initial wave of lymphopoiesis contribute to fetal and/or adult immunity remain to be determined.…”

“…Furthermore, the potential of adult marrow stem and progenitor cells to produce B-1a B cells is limited as discussed in reviews from Montecino-Rodriquez and Dorshkind 18 and Koybayashi and Yoshimoto. 12 The latter reviews discuss the controversy regarding postnatal B-1 B cell development in light of studies showing the potential of adult marrow to generate those cells. The issue is not whether B-1 B cells, and B-1a B cells in particular, can develop from precursors in adult marrow but the efficiency with which they do so, and those reviews make the point that B-1 output from adult precursors is significantly attenuated compared to fetal progenitors.…”

Efficient enzyme-free method to assess the development and maturation of the innate and adaptive immune systems in the mouse colon

“…The immune system begins its development during embryogenesis, playing a crucial role in protecting the developing fetus from neonatal infections 10 – 12 . Initially, the fetal immune system primarily consists of primitive immune cells, including immature T and B lymphocytes, natural killer cells, monocytes, macrophages and dendritic cells 13 – 17 . As embryonic development progresses, the immune system undergoes diversification and specialization, enabling it to respond to encountered antigens 10 , 18 .…”

Transient PU.1 low fetal progenitors generate lymphoid progeny that contribute to adult immunity

“…Lymphocyte development initiates in utero and continues after birth in the bone marrow and thymus ( Montecino-Rodriguez & Dorshkind, 2012 ; Kobayashi & Yoshimoto, 2023 ), but lymphopoiesis is not a linear process. Instead, hematopoietic stem cells (HSCs), multipotential progenitors, and more restricted progenitors with lymphoid potential emerge in multiple, overlapping waves of development ( Patel et al, 2022 ; Kobayashi et al, 2023 ).…”