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B Cell Subsets (b + cell_subset)

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Medical Sciences100%

Selected Abstracts

Prolactin alters the mechanisms of B cell tolerance induction

ARTHRITIS & RHEUMATISM, Issue 6 2009
Subhrajit Saha
Objective Autoimmune diseases predominantly affect women, suggesting that female sex hormones may play a role in the pathogenesis of such diseases. We have previously shown that persistent mild-to-moderate elevations in serum prolactin levels induce a break in self tolerance in mice with a BALB/c genetic background. The aim of this study was to evaluate the effects of hyperprolactinemia on the mechanisms of B cell tolerance induction. Methods Effects of prolactin on splenic B cell subsets were studied in female BALB/c mice. B cell receptor (BCR),mediated apoptosis and proliferation of transitional B cells were analyzed by flow cytometry. Expression of apoptotic genes was examined by microarrays and real-time polymerase chain reaction analysis. B cells coexpressing ,/, light chains were assessed by flow cytometry and immunohistochemistry. Activation status of transitional type 3 (T3) B cells was evaluated by BCR-induced calcium influx studies. Results BCR-mediated apoptosis of the T1 B cell subset, a major checkpoint for negative selection of autoreactive specificities, was decreased in prolactin-treated mice. Microarray studies indicated that this event may be mediated by the prolactin-induced up-regulation of the antiapoptotic gene interferon-, receptor type II and down-regulation of the proapoptotic gene Trp63. Prolactin treatment also altered the amount of receptor editing, as indicated by the increased number of transitional B cells coexpressing ,/, light chains. Additionally, hyperprolactinemia modified the level of B cell anergy by increasing the degree of BCR-induced calcium influx in the T3 B cells. Conclusion Persistently elevated serum prolactin levels interfere with B cell tolerance induction by impairing BCR-mediated clonal deletion, deregulating receptor editing, and decreasing the threshold for activation of anergic B cells, thereby promoting autoreactivity. [source]

Pyoderma Gangrenosum in Association with Autoimmune Neutropenia of Infancy

PEDIATRIC DERMATOLOGY, Issue 6 2008
Anisha J. Mehta M.R.C.P.
Histology showed changes consistent with pyoderma gangrenosum and the ulcer resolved rapidly with super-potent topical steroids under occlusion. Blood tests revealed a persistent neutropenia. Immunoglobulin G (IgG) antineutrophil antibodies were detected in the serum, directed against human neutrophil antigen (HNA)-1a. Bone marrow studies showed normocellular marrow with no evidence of dysplasia. T and B cell subsets and karotype analysis were normal. Autoimmune neutropenia is an uncommon self-limiting condition in young children. Pyoderma gangrenosum is rare in infants, although the buttocks are a common site of involvement in this age group. Pyoderma gangrenosum in infancy can be associated with systemic disease as in adults, particularly myelodysplasia and leukemia, arthritis and inflammatory bowel disease. However, the association of pyoderma gangrenosum and autoimmune neutropenia of infancy has not previously been reported. [source]

Interferon-,,dependent inhibition of B cell activation by bone marrow,derived mesenchymal stem cells in a murine model of systemic lupus erythematosus

ARTHRITIS & RHEUMATISM, Issue 9 2010
Francesca Schena
Objective Bone marrow,derived mesenchymal stem cells (BM-MSCs) are multipotent cells characterized by immunomodulatory properties and are therefore considered a promising tool for the treatment of immune-mediated diseases. This study was undertaken to assess the influence of murine BM-MSCs on the activation of B cells in (NZB × NZW)F1 mice as an animal model of systemic lupus erythematosus (SLE). Methods We evaluated the in vitro effects of BM-MSCs on the proliferation and differentiation to plasma cells of splenic mature B cell subsets, namely follicular and marginal zone B cells isolated from (NZB × NZW)F1 mice. Lupus mice were also treated with BM-MSCs, and serum autoantibodies, proteinuria, histologic changes in the kidney, and survival rates were monitored. Results BM-MSCs inhibited antigen-dependent proliferation and differentiation to plasma cells of follicular and marginal zone B cells in vitro. This inhibitory effect was dependent on interferon-, (IFN,) and was mediated by cell-to-cell contact, involving the programmed death 1 (PD-1)/PD ligand pathway. In vivo treatment with BM-MSCs did not affect the levels of anti,double-stranded DNA antibodies or proteinuria. However, a reduction in glomerular immune complex deposition, lymphocytic infiltration, and glomerular proliferation was observed. Conclusion Our findings indicate that BM-MSCs affect B cell receptor,dependent activation of both follicular and marginal zone B cells from lupus mice. This inhibitory effect is IFN,-dependent and cell contact,dependent. MSCs in vivo do not affect the production of autoantibodies, the level of proteinuria, or the mortality rates. Nonetheless, the significant improvement in histologic findings in the kidney supports the potential role of MSCs in the prevention of glomerular damage. [source]

Prolactin alters the mechanisms of B cell tolerance induction

ARTHRITIS & RHEUMATISM, Issue 6 2009
Subhrajit Saha
Objective Autoimmune diseases predominantly affect women, suggesting that female sex hormones may play a role in the pathogenesis of such diseases. We have previously shown that persistent mild-to-moderate elevations in serum prolactin levels induce a break in self tolerance in mice with a BALB/c genetic background. The aim of this study was to evaluate the effects of hyperprolactinemia on the mechanisms of B cell tolerance induction. Methods Effects of prolactin on splenic B cell subsets were studied in female BALB/c mice. B cell receptor (BCR),mediated apoptosis and proliferation of transitional B cells were analyzed by flow cytometry. Expression of apoptotic genes was examined by microarrays and real-time polymerase chain reaction analysis. B cells coexpressing ,/, light chains were assessed by flow cytometry and immunohistochemistry. Activation status of transitional type 3 (T3) B cells was evaluated by BCR-induced calcium influx studies. Results BCR-mediated apoptosis of the T1 B cell subset, a major checkpoint for negative selection of autoreactive specificities, was decreased in prolactin-treated mice. Microarray studies indicated that this event may be mediated by the prolactin-induced up-regulation of the antiapoptotic gene interferon-, receptor type II and down-regulation of the proapoptotic gene Trp63. Prolactin treatment also altered the amount of receptor editing, as indicated by the increased number of transitional B cells coexpressing ,/, light chains. Additionally, hyperprolactinemia modified the level of B cell anergy by increasing the degree of BCR-induced calcium influx in the T3 B cells. Conclusion Persistently elevated serum prolactin levels interfere with B cell tolerance induction by impairing BCR-mediated clonal deletion, deregulating receptor editing, and decreasing the threshold for activation of anergic B cells, thereby promoting autoreactivity. [source]

Effects of anti-CD154 treatment on B cells in murine systemic lupus erythematosus

ARTHRITIS & RHEUMATISM, Issue 2 2003
Xiaobo Wang
Objective To determine the immunologic effects of anti-CD154 (CD40L) therapy in the (NZB × NZW)F1 mouse model of systemic lupus erythematosus. Methods Twenty-week-old and 26-week-old (NZB × NZW)F1 mice were treated with continuous anti-CD154 therapy. Mice were followed up clinically, and their spleens were studied at intervals for B and T cell numbers and subsets and frequency of anti,double-stranded DNA (anti-dsDNA),producing B cells. T cell,dependent immunity was assessed by studying the humoral response to the hapten oxazolone. Results IgG anti-dsDNA antibodies decreased during therapy and disease onset was delayed, but immune tolerance did not occur. During treatment, there was marked depletion of CD19+ cells in the spleen; however, autoreactive IgM-producing B cells could still be detected by enzyme-linked immunospot assay. In contrast, few IgG- and IgG anti-dsDNA,secreting B cells were detected. Eight weeks after treatment cessation, the frequency of B cells producing IgG anti-dsDNA antibodies was still decreased in 50% of the mice, and activation and transition of T cells from the naive to the memory compartment were blocked. Anti-CD154 treatment blocked both class switching and somatic mutation and induced a variable period of relative unresponsiveness of IgG anti-dsDNA,producing B cells, as shown by decreased expression of the CD69 marker and failure to generate spontaneous IgG anti-dsDNA,producing hybridomas. Treated mice mounted an attenuated IgM response to the hapten oxazolone and produced no IgG antioxazolone antibodies. Conclusion Anti-CD154 is a B cell,depleting therapy that affects multiple B cell subsets. Activation of both B and T cells is prevented during therapy. After treatment cessation, autoreactive B cells progress through a series of activation steps before they become fully competent antibody-producing cells. The general immunosuppression induced during treatment will need to be taken into account when using B cell,depleting regimens in humans. [source]