During the postnatal development, astrocytic cells in the neocortex progressively lose their neural stem cell (NSC) potential, whereas this peculiar attribute is preserved in the adult subventricular zone (SVZ). To understand this fundamental difference, many reports suggest that adult subventricular GFAP-expressing cells might be maintained in immature developmental stage. Here, we show that S100B, a marker of glial cells, is absent from GFAP-expressing cells of the SVZ and that its onset of expression characterizes a terminal maturation stage of cortical astrocytic cells. Nevertheless, when cultured in vitro, SVZ astrocytic cells developed as S100B expressing cells, as do cortical astrocytic cells, suggesting that SVZ microenvironment represses S100B expression. Using transgenic s100b-EGFP cells, we then demonstrated that S100B expression coincides with the loss of neurosphere forming abilities of GFAP expressing cells. By doing grafting experiments with cells derived from beta-actin-GFP mice, we next found that S100B expression in astrocytic cells is repressed in the SVZ, but not in the striatal parenchyma. Furthermore, we showed that treatment with epidermal growth factor represses S100B expression in GFAP-expressing cells in vitro as well as in vivo. Altogether, our results indicate that the S100B expression defines a late developmental stage after which GFAP-expressing cells lose their NSC potential and suggest that S100B expression is repressed by adult SVZ microenvironment.

B- and T-lymphocyte populations have an independent homeostatic regulation of resting (B and T) and activated (B) or memory (T) cell compartments. This organization may provide an efficient mechanism to ensure simultaneously a first natural barrier of protection against common pathogens, the maintenance of immunological T-cell memory and a reservoir of repertoire diversity capable of dealing with new antigenic challenges.

We studied the role of bone marrow B cell production in the renewal of peripheral B cells and the feedback mechanisms that control the entry of newly formed B cells into the peripheral B cell pools. When resting lymph node B cells are injected into B cell–deficient hosts, a fraction of the transferred cells expands and constitutes a highly selected population that survives for prolonged periods of time by continuous cell renewal at the periphery. Although the number of donor B cells recovered is low, a significant fraction shows an activated phenotype, and the serum immunoglobulin (Ig)M levels are as in normal mice. This population of activated B cells is resistant to replacement by a new cohort of B cells and is able to feedback regulate both the entry of newly formed B cells into the peripheral pool and terminal differentiation. These findings suggest that peripheral B cell selection follows the first come, first served rule and that IgM-secreting cells are generated from a pool of stable activated B cells with an independent homeostasis.

SummaryThe immune response of T lymphocytes to pathogens is initiated in draining secondary lymphoid organs, and activated cells then migrate to the site of infection. Thus, control of naïve and regulatory CD4 + T-cell migration is crucial; however, it is poorly understood in physiological and pathological conditions. We found that CD4 + subpopulations displayed characteristic regulator of G-protein signalling (RGS) gene expression profiles. Regulatory T cells express higher levels of RGS1, RGS9 and RGS16 than naïve cells. These genes are up-regulated upon cell activation and their level of expression correlates with in vivo cell migration. Using parabiosis, we showed that regulatory T lymphocytes migrate less than naïve T cells and that migrant naïve T cells express even lower RGS levels than their static counterparts. Our results show an inverse correlation between the capacity to migrate and the levels of RGS1, RGS9 and RGS16 for both naïve and regulatory T cells. Taken together, these results suggest a role for RGS molecules in chemokine-induced lymphocyte migration and demonstrate the peculiarity of regulatory T cells in terms of phenotype and migration ability, providing new insights into their function.

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Cellular competition for survival signals offers a cogent and appealing mechanism for the maintenance of cellular homeostasis [Raff, M. C. (1992) Nature (London) 356, 397-400]. We present a theoretical and experimental investigation of the role of competition for resources in the regulation of peripheral B cell numbers. We use formal ecological competition theory, mathematical models of interspecific competition, and competitive repopulation experiments to show that B cells must compete to persist in the periphery and that antigen forms a part of the resources over which B cells compete.''The most basic qualities of a natural community are the kinds and numbers of species living in them.'' This quotation from a classic ecological monograph (1) could equally well apply to immunology, where the communities in question are populations of lymphocytes present within individual organisms. Motivated by this similarity in basic questions we have used ecological competition theory in studies of B cell homeostasis and diversity. A combination of laboratory and mathematical models lead us to propose that the size of the peripheral B lymphocyte pool results from a process of immigration from the bone marrow, competition for resources in the periphery (2), and rapid death of cells that fail to secure resources. Our models allow us to quantify the contribution of each of these three processes to the final size of the peripheral B cell pool.Immunologists often use the word competition and most would probably agree that they define competition as ''an interaction between two populations, in which, for each, the birth rates are depressed or the death rates increased by the presence of the other population'' (3). However, this type of interaction can arise through a number of different processes. In resource competition (1) the negative effects come about because the two populations both have a need for the same substrate that is in limited supply. In apparent competition (4) the two populations affect each others' growth via a shared predator rather than a shared resource. Other schemes have been proposed where populations affect each other directly or indirectly via populations on the same trophic level (5). It is useful to be precise about which type of process is envisaged when competition is invoked. Because such a formalism already exists in the ecological literature, it makes sense to adapt it to the special situation of cells competing within an organism. To go further and ask ''does the formalism fit the data?'' it becomes necessary to express the formal model in mathematical equations and see if those equations behave like the populations that we observe. This is the strategy we have adopted in the work presented here. We have developed formal schemes for competition among B lymphocytes that give rise to two models; one of competition in its broadest sense and one that is specifically a model of resource competition. We show detailed comparisons of our first model with our data on B lymphocyte population dynamic...

In pre-Tα (pTα) gene-deleted mice, the positively selectable CD4+CD8+ double-positive thymocyte pool is only 1% that in wild-type mice. Consequently, their peripheral T cell compartment is severely lymphopenic with a concomitant increase in proportion of CD25+FoxP3+ regulatory T cells. Using mixed bone marrow chimeras, where thymic output was 1% normal, the pTα−/− peripheral T cell phenotype could be reproduced with normal cells. In the pTα−/− thymus and peripheral lymphoid organs, FoxP3+CD4+ cells were enriched. Parabiosis experiments showed that many pTα−/−CD4+ single-positive thymocytes represented recirculating peripheral T cells. Therefore, the enrichment of FoxP3+CD4+ single-positive thymocytes was not solely due to increased thymic production. Thus, the pTα−/− mouse serves as a model system with which to study the consequences of chronic decreased thymic T cell production on the physiology of the peripheral T cell compartment.

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