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James B Chung

Publications and source records attributed to James B Chung.

6 recordsLinked to original sources
PubMed2003

Incomplete activation of CD4 T cells by antigen-presenting transitional immature B cells: implications for peripheral B and T cell responsiveness.

B cells leave the bone marrow as transitional B cells. Transitional B cells represent a target of negative selection and peripheral tolerance, both of which are abrogated in vitro by mediators of T cell help. In vitro, transitional and mature B cells differ in their responses to B cell receptor ligation. Whereas mature B cells up-regulate the T cell costimulatory molecule CD86 (B7.2) and are activated, transitional B cells do not and undergo apoptosis. The ability of transitional B cells to process and present Ag to CD4 T cells and to elicit protective signals in the absence of CD86 up-regulation was investigated. We report that transitional B cells can process and present Ag as peptide:MHC class II complexes. However, their ability to activate T cells and elicit help signals from CD4-expressing Th cells was compromised compared with mature B cells, unless exogenous T cell costimulation was provided. A stringent requirement for CD28 costimulation was not evident in interactions between transitional B cells and preactivated CD4-expressing T cells, indicating that T cells involved in vivo in an ongoing immune response might rescue Ag-specific transitional B cells from negative selection. These data suggest that during an immune response, immature B cells may be able to sustain the responses of preactivated CD4(+) T cells, while being unable to initiate activation of naive T cells. Furthermore, the ability of preactivated, but not naive T cells to provide survival signals to B cell receptor-engaged transitional immature B cells argues that these B cells may be directed toward activation rather than negative selection when encountering Ag in the context of a pre-existing immune response.

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PubMed2003

Transitional B cells: step by step towards immune competence.

Transitional B cells mark the crucial link between bone-marrow (BM) immature and peripheral mature B cells. Examination reveals unexpected heterogeneity, consisting of contiguous subsets with phenotypic and functional differences. Data point to the late transitional B-cell stage as a crucial juncture at which developing B cells gain access to splenic follicles, become responsive to T-cell help and lose sensitivity to negative selection, characterizing the immature B-cell response to B-cell antigen receptor (BCR) signaling in vitro and in vivo. The biological and molecular processes directing maturation through this stage are becoming clearer through biochemical studies and murine models deficient in various components of the BCR signaling pathway.

Animals↗
PubMed2002

Cost-effectiveness analysis of the Lyme disease vaccine.

OBJECTIVE: A vaccine for Lyme disease was approved in 1998 for use in the US. Given the high cost of the vaccine, the low risk of Lyme disease in many areas, and the largely curable nature of the disease, the cost-effectiveness of the vaccine in various risk groups is uncertain. This study was undertaken to examine the cost-effectiveness of the Lyme disease vaccine and the factors that influence its cost-effectiveness. METHODS: We constructed a Markov decision-analysis model to evaluate the clinical effectiveness and cost-effectiveness of the Lyme disease vaccine in populations at various levels of risk for the disease. The probabilities of clinical events and costs were estimated from reports in the literature. Sensitivity analyses assessed the impact of potential variations of parameters on model results. RESULTS: At the average national incidence of Lyme disease (0.0067%), the incremental cost-effectiveness of vaccination was approximately $1,600,000 per case averted when a yearly booster was given for 10 years after the standard initial vaccination regimen of 3 inoculations at 0, 1, and 12 months. For populations with an annual Lyme disease incidence of 1% (the incidence in several well-defined geographical areas of the US), the incremental cost-effectiveness was approximately $9,900 per case averted. Disease incidence had to exceed 10% before vaccination with yearly boosters became both more effective and more cost saving than no vaccination. CONCLUSION: The Lyme disease vaccine is cost-effective only for individuals who live in areas where Lyme disease is endemic and who are frequently exposed to ticks.

Cost-Benefit Analysis↗
PubMed2002

CD23 defines two distinct subsets of immature B cells which differ in their responses to T cell help signals.

Transitional immature B cells undergo apoptosis and fail to proliferate in response to BCR cross-linking, thus representing a target for negative selection of potentially autoreactive B cells in vivo. In agreement with recent reports, transitional B cells were divided into developmentally contiguous subsets based on their surface expression of CD23. When transferred, CD23(+) transitional B cells readily localized to the splenic follicles and the outer PALS. Compared with CD23(-) transitional B cells, CD23(+) transitional B cells proliferated more vigorously and were rescued from BCR-induced apoptosis to a greater degree, by T cell help signals. However, both CD23(-) and CD23(+) transitional B cells failed to up-regulate CD86 (B7-2) in response to BCR ligation. These findings demonstrate that phenotypically defined subsets within the transitional B cell population are functionally distinct. Specifically, responsiveness to T cell help is a late acquisition corresponding to the stage when the B cells gain access to peripheral compartments enriched in antigen and activated T cells. The failure of transitional B cells to up-regulate CD86 to BCR-mediated stimulation suggests a unique interaction between transitional B cells and T cells with implications for tolerance in the T cell compartment.

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