Fetal Lymphoid Progenitors Become Restricted to B-1 Fates Coincident with IL-7Rα Expression.

B-1 cells represent a sub-fraction of B lymphocytes that participate in T cell-independent antibody production and contribute to innate immunity. While the production of B-1 cells is favored during the fetal waves of lymphopoiesis, it has been unclear when and how that differentiation option is specified. To clarify this, lymphoid and hematopoietic progenitors of fetal liver (FL) and adult bone marrow (ABM) were examined for the B cell differentiation potential.

BANK1 Regulates IgG Production in a Lupus Model by Controlling TLR7-Dependent STAT1 Activation.

The purpose of our study was to investigate the effects of the adaptor Bank1 in TLR7 signaling using the B6.Sle1.yaa mouse, a lupus model that develops disease through exacerbated TLR7 expression.

Stem and progenitor cell subsets are affected by JAK2 signaling and can be monitored by flow cytometry.

Although extremely rare, hematopoietic stem cells (HSCs) are divisible into subsets that differ with respect to differentiation potential and cell surface marker expression. For example, we recently found that CD86(-) CD150(+) CD48(-) HSCs have limited potential for lymphocyte production. This could be an important new tool for studying hematological abnormalities.

RAG-1 and Ly6D independently reflect progression in the B lymphoid lineage.

Common lymphoid progenitors (CLPs) are thought to represent major intermediates in the transition of hematopoietic stem cells (HSCs) to B lineage lymphocytes. However, it has been obvious for some time that CLPs are heterogeneous, and there has been controversy concerning their differentiation potential. We have now resolved four Flt3(+) CLP subsets that are relatively homogenous and capable of forming B cells.

The Satb1 protein directs hematopoietic stem cell differentiation toward lymphoid lineages.

How hematopoietic stem cells (HSCs) produce particular lineages is insufficiently understood. We searched for key factors that direct HSC to lymphopoiesis. Comparing gene expression profiles for HSCs and early lymphoid progenitors revealed that Satb1, a global chromatin regulator, was markedly induced with lymphoid lineage specification.

Early events in lymphopoiesis: an update.

Purpose Of Review: Cells of the immune system are replaced in large numbers throughout life, and the underlying mechanisms have been extensively studied. Whereas the pace of discovery in this area is unprecedented, many questions remain, particularly with respect to lymphocyte formation.

Recent Findings: While transcription factors have long been a focus of investigation, microRNAs are also being implicated in lymphopoiesis.

Bone marrow endothelial progenitors augment atherosclerotic plaque regression in a mouse model of plasma lipid lowering.

The major event initiating atherosclerosis is hypercholesterolemia-induced disruption of vascular endothelium integrity. In settings of endothelial damage, endothelial progenitor cells (EPCs) are mobilized from bone marrow into circulation and home to sites of vascular injury where they aid endothelial regeneration. Given the beneficial effects of EPCs in vascular repair, we hypothesized that these cells play a pivotal role in atherosclerosis regression.

Nuclear transferred embryonic stem cells for analysis of B1 B-lymphocyte development.

The transfer of nuclei of fully differentiated cells into enucleated oocytes is a well-recognized method for the generation of embryonic stem (ES) cells. Here, we demonstrate that nuclear transferred ES (NT-ES) cells can be established with high efficiency using innate-like B lymphocytes as donor cells. We established two mouse lines carrying rearranged immunoglobulin heavy and light chains using NT-ES cells containing nuclei from peritoneal cavity B1 cells.

CD86 is expressed on murine hematopoietic stem cells and denotes lymphopoietic potential.

A unique subset of CD86(-) HSCs was previously discovered in mice that were old or chronically stimulated with lipopolysaccharide. Functionally defective HSCs were also present in those animals, and we now show that CD86(-) CD150(+) CD48(-) HSCs from normal adult mice are particularly poor at restoring the adaptive immune system. Levels of the marker are high on all progenitors with lymphopoietic potential, and progressive loss helps to establish relations between progenitors corresponding to myeloid and erythroid lineages.

Replenishing B lymphocytes in health and disease.

The path from hematopoietic stem cells (HSCs) to functional B lymphocytes has long been appreciated as a basic model of differentiation, but much clinically relevant information has also been obtained. It is now possible to conduct single cell studies with increasingly high resolution, revealing that individual stem and progenitor cells differ from each other with respect to differentiation potential and fates. B lymphopoiesis is now seen as a gradual and unsynchronized process where progenitors eventually become B lineage restricted.

In vivo expansion of CD4+Foxp3+ regulatory T cells mediated by GITR molecules.

CD4(+)Foxp3(+) regulatory T cells (Treg cells) play an important role in maintaining self-tolerance as suppressive/regulatory CD4 T cells. In vitro analyses have revealed the characteristics of Treg cells, that is, hyporesponsiveness when stimulated via TCR in the presence of splenic APC. In this study, we report a new mAb, G3c, which can induce the expansion of Treg cells stimulated with anti-CD3 Ab along with splenic APC, the culture conditions in which Treg cells exhibit hyporesponsiveness.

Antigen-independent generation of a unique CD4 T cell-subset with aging and its persistent unresponsiveness.

Aging leads to a decline in the reactivity of CD4 T cells, in humans and mice. However, we have reported that not all CD4 T cells in aged mice were hyporesponsive, that is, a particular subset maintained the ability to mount a normal response. In this study, we examined the possibility of recalling reactivity in the hyporesponsive CD4 T cell-subset in aged mice.

CD4+CD25+Foxp3+ T cells and CD4+CD25-Foxp3+ T cells in aged mice.

Aging is associated with a progressive decline in T cell-mediated immune responses. However, it has been unknown whether regulatory/suppressive CD4 T cells are involved in this decline. Our in vitro analyses revealed that CD4+CD25+ T cells, the well-characterized naturally occurring regulatory/suppressive CD4 T cells, in aged mice are functionally comparable to those in young mice (i.

Cross-linking of CD45 on suppressive/regulatory T cells leads to the abrogation of their suppressive activity in vitro.

CD4(+)CD25(+) T cells have immunoregulatory and suppressive functions and are responsible for suppressing self-reactive cells and maintaining self-tolerance. In addition to CD4(+)CD25(+) T cells, there is some evidence that a fraction of CD4(+)CD25(-) T cells exhibit suppressive activity in vitro or in vivo. We have shown, using aged mice, that aging not only leads to a decline in the ability to mount CD4(+)CD25(-) T cell responses, but, at the same time, renders aged CD4(+)CD25(-) T cells suppressive.

Expression profiling with arrays of randomly disrupted genes in mouse embryonic stem cells leads to in vivo functional analysis.

DNA arrays are capable of profiling the expression patterns of many genes in a single experiment. After finding a gene of interest in a DNA array, however, labor-intensive gene-targeting experiments sometimes must be performed for the in vivo analysis of the gene function. With random gene trapping, on the other hand, it is relatively easy to disrupt and retrieve hundreds of genes/gene candidates in mouse embryonic stem (ES) cells, but one could overlook potentially important gene-disruption events if only the nucleotide sequences and not the expression patterns of the trapped DNA segments are analyzed.