Immunosuppressive Property within the Streptococcus pneumoniae Cell Wall That Inhibits Generation of T Follicular Helper,Germinal Center,and Plasma Cell Response to a Coimmunized Heterologous Protein

We previously demonstrated that intact, inactivated Streptococcus pneumoniae (unencapsulated strain R36A) inhibits IgG responses to a number of coimmunized soluble antigens (Ags). In this study, we investigated the mechanism of this inhibition and whether other extracellular bacteria exhibited similar effects. No inhibition was observed if R36A was given 24 h before or after immunization with soluble chicken ovalbumin (cOVA), indicating that R36A acts transiently during the initiation of the immune response. Using transgenic cOVA-specific CD4⁺ T cells, we observed that R36A had no significant effect on T-cell activation (24 h) or generation of regulatory T cells (day 7) and only a modest effect on T-cell proliferation (48 to 96 h) in response to cOVA. However, R36A mediated a significant reduction in the formation of Ag-specific splenic germinal center T follicular helper (GC Tfh) and GC B cells and antibody-secreting cells in the spleen and bone marrow in response to cOVA or cOVA conjugated to 4-hydroxy-3-nitrophenylacetyl hapten (NP-cOVA). Of note, the inhibitory effect of intact R36A on the IgG anti-cOVA response could be reproduced using R36A-derived cell walls. In contrast to R36A, neither inactivated, unencapsulated, intact Neisseria meningitidis nor Streptococcus agalactiae inhibited the OVA-specific IgG response. These results suggest a novel immunosuppressive property within the cell wall of Streptococcus pneumoniae.     

T Follicular Helper Cell-Germinal Center B Cell Interaction Strength Regulates Entry into Plasma Cell or Recycling Germinal Center Cell Fate

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Apoptosis and the B Cell Response to Antigen

The primary B cell response to T cell dependent antigens comprises two pathways of differentiation; one resulting in formation of foci of antibody forming cells in the extrafollicular regions of secondary lymphoid organs and the other giving rise to germinal centers within the follicles. Foci of antibody forming cells are detectable for only a limited time, before involuting due to apoptosis of the plasma cells. Similarly in the germinal center, regulation of cell number, selection of high affinity variants generated by somatic hypermutation, and the resolution of the germinal center itself all involve the death of unwanted B cells. In this review, we describe recent experiments which have allowed determination of the role of certain forms of apoptosis in the B cell response to antigen.     

Follicular Dendritic Cell Activation by TLR Ligands Promotes Autoreactive B Cell Responses

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Seminal Plasma Abrogates the Postcoital T Cell Response to Spermatozoal Histocompatibility Antigens

ABSTRACT: The T-cell responses to spermatozoal histocompatibility antigens were studied in the uterine regional lymph nodes of female rats by a specific cytoadhesion assay. The antigenic challenge was introduced either by artificial insemination with syngeneic or allogeneic epididymal spermatozoa or coitus. The uterine regional T-cell response to allogeneic spermatozoa following artificial insemination was measurable after 2 days and continued undiminished until day 5. In contrast, the measurable response to allogeneic coital challenge peaked on day 3 and disappeared by days 4–5. Since the difference between the two stimuli involved the presence of seminal plasma, these results indicate a possible immunoregulatory (suppressive) effect of seminal plasma on the cellular immune reaction of the female to the male alloantigens after mating.     

Transcriptional Regulation of Germinal Center B and Plasma Cell Fates by Dynamical Control of IRF4

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Outcomes of Hematopoietic Cell Transplantation for Diffuse Large B Cell Lymphoma Transformed from Follicular Lymphoma

There are limited data on the outcomes of autologous or allogeneic hematopoietic cell transplantation (HCT) in diffuse large B cell lymphoma transformed from follicular lymphoma. We analyzed transplantation outcomes in 141 subjects with biopsy-proven diffuse large B-cell lymphoma transformed from follicular lymphoma reported to the Center for International Blood and Marrow Transplant Research between 1990 and 2009. Two groups were identified: autologous HCT (auto-HCT; n = 108) and allogeneic HCT (allo-HCT; n = 33). Fewer auto-HCTs were done for transformed follicular lymphoma in 2003 to 2009, with a shift favoring allo-HCT. Auto-HCT was associated with a 1-year nonrelapse mortality (NRM) of 8% (95% confidence interval [CI], 4% to 14%), 5-year progression-free survival of 35% (95% CI, 26% to 45%), and 5-year overall survival of 50% (95% CI, 40% to 59%). In contrast, allo-HCT was associated with a 1-year NRM of 41% (95% CI, 23% to 58%), 5-year progression-free survival of 18% (95% CI, 6% to 35%), and 5-year overall survival of 22% (95% CI, 8% to 41%). Auto-HCT for transformed follicular lymphoma achieves sustained remission in a high proportion of subjects. The high NRM of allo-HCT offset any benefit that might be associated with this transplantation modality.     

Regulation of the Immune Response to Hepatitis B Virus and Human Serum Albumin

The circulatory pool of B cells, from donors immune lo hepatitis B (HB) through natural infection, contained sensitized B cells with the capacity to secrete antibodies with specificity for human serum albumin (USA) when stimulated with purified hepatitis B surface antigen (HBsAg) in vitro The immunoglobulin secretion was dependent upon and regulated by T cells and specifically induced, since it was not obtained in cell cultures from HB-susceptible donors. Culture supernatants with anti-USA reactivity also contained specific antibodies to HBsAg (anti-HBs). indicating that the outer coat of HBV normally provokes an immune response to both the viral antigen and a self component. Perturbation in the regulation of the immune response triggered by USA in association with HBV/HBsAg particles may involve a putative risk for development of chronic HBsAg carriership.     

Role of Antigen in the Regulation of the Immune Response to Dextran B512

Dextranase mixed with dextran in vitro or injected into mice before the antigen abolished the immunogenicity of both thymus-dependent and thymus-independent forms of dextran. Dextranase could degrade dextran in vivo even when given 6-15 days after the antigen. Dextranase injected after the antigen suppressed the immune response when given 24 h, but not 48 h, after the antigen, indicating that the antigen must interact with the immune system for 48 h to initiate a response. Thereafter , the B cells are independent of further antigen stimulation. The induction of autoanti -idiotypic anti-dextran antibodies was abolished if dextranase was given 24 h, but not 48 h, after the antigen, indicating that anti-idiotypic antibodies can be induced in the absence of antigen or immune complexes once anti-dextran antibodies have been synthesized.     

Regulation of the Immune Response to Hepatitis B Virus and Human Serum Albumin

Peripheral B and T cells sensitized to human serum albumin (HSA) were found in a cohort of patients chronically infected with hepatitis B virus (HBV). Throughout this study, two groups of symptomatic chronic hepatitis B surface antigen (HBsAg) carriers could be distinguished, characterized by divergent T-cell regulation of the spontaneous IgG anti-HSA secretion. Patients in a quiescent phase of the disease [patients with chronic persistent hepatitis B (CPH), anti-HBe reactivity and absence of viral replication, group A] had circulatory in vivo HBsAg-HSA preactivated B cells with the capacity to secrete spontaneously IgG antibodies with specificity for HSA when isolated and cultured. The addition of autologous T lymphocytes at a T/B-cell ratio of 8.0 suppressed the spontaneous anti-HSA secretion. In contrast, patients in an active stage of the disease exhibited in vivo preactivated T cells exerting helper cell functions on the spontaneous IgG anti-HSA secretion. Memory T cells, sensitized to low concentrations of HBsAg-HSA with disparate regulatory functions, were also detectable in the two groups of patients.     

Follicular Dendritic Cell Sarcoma of the Tonsil

Follicular dendritic cell sarcoma (FDCS) is unusual, and those with an extranodal origin in the head and neck region are extremely rare. To date, no cases of tumors featuring the characteristics of follicular dendritic cells were reported in Korea. We report a new case of FDCS of the tonsils in a 65-year-old man. A diagnostic tonsillectomy was performed. Based on histopathologic and immunohistochemical findings, the patient was diagnosed with FDCS. Adjuvant radiotherapy was performed due to a high mitotic count. The patient survived with a 2-year disease free period. The differential diagnosis of a tonsillar mass must include FDCS. In cases in which FDCS is suspected on histopathologic examination, an immunohistochemical study is essential for the diagnosis     

Regulation of B Cell:T Cell Interactions: Potential Involvement of an Endogenous B Cell Sialidase

In light of the ability of B cells treated with neuraminidase to interact more effectively with T cells, the increased capacity of activated, but not small resting B cells, to interact with T cells could be associated with the level of sialylation on certain B cell surface molecules which influences the effectiveness of the physical interaction between B and T cells. The purpose of this study was to determine if activation of B cells altered sialylation via an endogenous sialidase which affected both the initial interaction between T and B cells and subsequent B cell-induced T cell proliferation. The competitive neuraminidase inhibitor, 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (NeuAc2en), inhibited LPS-mediated enhancement of B cell conjugate formation with Ia-specific T cell clones as well as enhancement of their capacity to stimulate a mixed lymphocyte reaction. The addition of NeuAc2en during LPS stimulation did not affect the surface expression of Ia, LFA-1, ICAM-1 or mB7, suggesting that inhibition of LPS-mediated enhancement by the sialidase inhibitor was not due to changes in the level of expression of the major B cell adhesion or co-stimulatory molecules. Short term stimulation with phorbol myristate acetate (PMA) and ionomycin also enhanced the ability of resting B cells to form antigen specific T:B conjugates. However, activation of B cells with PMA and ionomycin or with LPS did not change the capacity of a sialic acid specific lectin to bind to the B cells, suggesting that activation was not associated with global changes in surface sialic acid content. B cell stimulation did not appear to increase the activity of the most prevalent B cell sialidase activity as measured in an in vitro assay system, suggesting that the major B cell sialidase may not be responsible for the alteration of B cell sialylation levels or the ability of activated B cells to interact more effectively with T cells. The possibility of intracellular compartmentalization of sialidase activity or that a minor B cell sialidase may play a role in the regulation of a B cells ability to interact with T cells are discussed.     

Regulation of B Cell:T Cell Interactions: Potential Involvement of an Endogenous B Cell Sialidase

In light of the ability of B cells treated with neuraminidase to interact more effectively with T cells, the increased capacity of activated, but not small resting B cells, to interact with T cells could be associated with the level of sialylation on certain B cell surface molecules which influences the effectiveness of the physical interaction between B and T cells. The purpose of this study was to determine if activation of B cells altered sialylation via an endogenous sialidase which affected both the initial interaction between T and B cells and subsequent B cell-induced T cell proliferation. The competitive neuraminidase inhibitor, 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (NeuAc2en), inhibited LPS-mediated enhancement of B cell conjugate formation with Ia-specific T cell clones as well as enhancement of their capacity to stimulate a mixed lymphocyte reaction. The addition of NeuAc2en during LPS stimulation did not affect the surface expression of Ia, LFA-1, ICAM-1 or mB7, suggesting that inhibition of LPS-mediated enhancement by the sialidase inhibitor was not due to changes in the level of expression of the major B cell adhesion or co-stimulatory molecules. Short term stimulation with phorbol myristate acetate (PMA) and ionomycin also enhanced the ability of resting B cells to form antigen specific T:B conjugates. However, activation of B cells with PMA and ionomycin or with LPS did not change the capacity of a sialic acid specific lectin to bind to the B cells, suggesting that activation was not associated with global changes in surface sialic acid content. B cell stimulation did not appear to increase the activity of the most prevalent B cell sialidase activity as measured in an in vitro assay system, suggesting that the major B cell sialidase may not be responsible for the alteration of B cell sialylation levels or the ability of activated B cells to interact more effectively with T cells. The possibility of intracellular compartmentalization of sialidase activity or that a minor B cell sialidase may play a role in the regulation of a B cells ability to interact with T cells are discussed.     

C Cell Carcinoma of the Thyroid Follicular variant

A case of C cell carcinoma of the thyroid with an unusual follicular growth pattern of the cancerous C cells is described. The primary tumor consisted of a mixture of medullary and follicular features while the metastatic foci in the lymph nodes and liver displayed only a medullary arrangement. Histochemical study disclosed numerous argyrophilic cells in both the follicular and medullary parts. These cells were immunohistochemically positive for calcitonin, calcitonin gene-related peptide (CGRP) and other peptides as well as carcinoembryonic antigen (CEA), but negative for thyroglobulin. Radioimmunoassay done on the tissue extract revealed a high content of calcitonin. Electron microscopy showed small intracytoplasmic secretory granules and, in the follicular lining cells, formation of microvilli. A minor component consisting of glandular structures has been reported in medullary carcinoma of the thyroid, suggesting a potentiality for glandular differentiation of the C cells. In equivocal cases, immuno-histochemical examination for calcitonin and thyroglobulin is essential for accurate diagnosis of thyroid carcinoma. Acta Pathol Jpn 39: 393-399, 1989.     

Increased T Cell Chemotaxis Response to Staphylococcus Enterotoxin B Mediated Human Endothelial Cell Damage In Vitro

The severity of superantigen (SAg)‐mediated shock is associated with T cell infiltration in major organs [ 1 , 2 ]. We postulated that endothelial cell inflammation and damage in sepsis might be mediated by chemotaxis and adherence of SAg‐activated T cells of vascular endothelium. We therefore investigate whether staphylococcal enterotoxin B (SEB) could modulate chemokine receptors expression on T cells as well as cytokine release, and then we examined the up‐modulation of chemokine‐associated affect on T cell‐mediated damage of endothelial cells. We consistently observed that SEB could upregulate expression of CCR5 on T cells and induce a panel of cytokines release from T cell, the latter could further induce increased release of chemokine such as MCP‐1, MIP‐1α and RANTES from human pulmonary artery endothelial cell (HPAEC). Both upregulation of CCR5 on SEB‐activated T cell and increased release of chemokine from HPAEC contribute to higher chemoattraction and adherence of T cell to HPAEC and ultimately led to more extensive endothelial damage. (These data suggest that T cell migration and acute inflammatory response in bacterial SAg‐mediated shock maybe explained partly by upregulation of chemotaxis of T cell of endothelium.) Revised as following: Our results demonstrate that upregulation of chemotaxis of T cell of endothelium is SEB specific, and this mechanism could account in part for T cell migration and acute inflammatory response in bacterial SAg‐mediated shock.