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G F Burton

Publications and source records attributed to G F Burton.

34 records · Page 2Linked to original sources
PubMed1995

Loss of follicular dendritic cells in murine-acquired immunodeficiency syndrome.

BACKGROUND: The disease caused by HIV-1 leads to the destruction of follicular dendritic cells (FDC) and the follicular architecture in secondary lymphoid tissues. The murine acquired immunodeficiency syndrome (MAIDS, caused by LP-BM5) serves as an animal model for study of mechanisms involved in development of retrovirus-induced immunodeficiencies. The present study was undertaken to determine whether LP-BM5 infection leads to the destruction of murine FDC and the normal follicular architecture in secondary lymphoid tissues. EXPERIMENTAL DESIGN: Mice were infected with LP-BM5, and the follicular architecture and FDC networks were assessed. The pathologic changes observed were correlated with FDC function. RESULTS: Three weeks after infection, FDC networks were present, and they often appeared hyperplastic. However, by 1 month after infection, distorted lymphoid follicles were apparent, and the intensity of FDC labeling began to decline. FDC disappeared first in the spleen, and in hyperimmunized mice, FDC in draining lymph nodes disappeared before FDC in nondraining lymph nodes. By 4 months, the normal follicular localization of B cells was missing, and FDC were not detectable in most tissues. As the FDC and the normal lymphoid architecture degenerated, extrafollicular foci of immunoblasts and plasma cells appeared in areas typically reserved for T cells, and the Thy 1.2+ T cells were dispersed. Of interest, the total number of Ig-producing cells increased as the disease progressed; in contrast, the number of anti-human serum albumin-producing cells in mice immunized with human serum albumin before infection decreased. CONCLUSIONS: These data indicate that, like HIV-1 infection, LP-BM5 infection leads to the loss of FDC and the normal follicular architecture. However, morphologic changes were not observed until after FDC had lost their normal ability to trap and retain Ag. These data indicate that retroviral infections may cause FDC dysfunctions long before FDC are destroyed.

Animals↗
PubMed1994

Follicular dendritic cell function and murine AIDS.

Infection of mice with LP-BM5 elicits an immunodeficiency state referred to as murine acquired immune deficiency syndrome (MAIDS). Shortly after infection, retrovirus particles become associated with follicular dendritic cells (FDC) and this study was undertaken to determine whether retroviruses alter FDC functions. The FDC functions examined included the ability to: (1) retain antigen (Ag) trapped prior to infection; (2) trap new Ag after infection; (3) maintain specific IgG responses; and (4) provide co-stimulatory signals to B cells. Mice were infected with LP-BM5 and the ability of their FDC to trap and retain 125I-Ag (HSA) was assessed. Serum anti-HSA levels were monitored and FDC co-stimulatory activity was indicated by increased B-cell proliferation. HSA trapped on FDC prior to infection began to disappear by 3 weeks and was practically gone by 6 weeks. Serum anti-HSA titres were maintained normally for about 3 weeks after infection and then declined precipitously. The ability of FDC to trap new Ag began to disappear around the second and third week of infection and was markedly depressed by the fourth week. However, FDC recovered from infected mice retained their ability to co-stimulate anti-mu- and interleukin-4 (IL-4)-activated B cells throughout a 5-week period. In short, the ability of FDC to trap and retain specific Ag and maintain specific antibody levels was markedly depressed after retrovirus infection. However, FDC from infected mice continued to provide co-stimulatory signals and these signals may contribute to the lymphadenopathy and splenomegaly characteristic of MAIDS.

Animals↗
PubMed1993

Induction of functional follicular dendritic cell development in severe combined immunodeficiency mice. Influence of B and T cells.

Ag injected into immune mice immediately complexes with specific antibody. Immune complexes not phagocytosed by macrophages are transported by Ag transport cells to lymph node follicles for trapping by follicular dendritic cells (FDC). These FDC serve as a long term repository of unprocessed Ag that is believed to maintain both B cell memory and the secondary antibody response. Severe combined immunodeficiency mice lack functional B cells and T cells. Consequently, this mutation also appears to affect the ability to produce Ag-retaining FDC. to assess B and T cell requirements for FDC development and function, severe combined immunodeficiency mice were reconstituted with BM, or mature B and T cells. The development of a FDC reticulum, a three-dimensional network produced by the intertwining of FDC dendrites was assessed by Ag trapping on FDC using the histochemically detectable Ag horseradish peroxidase and quantitated by morphometry. The results showed that bone marrow transplants or B and T cells transferred together supply the required elements for the development of severe combined immunodeficiency FDC reticula that function in Ag trapping and the induction of the germinal center. In contrast, B cells or T cells injected separately induced a minimal development of FDC reticulum. The B and T cell requirements demonstrated here strongly indicate that B-T cell collaboration and the factors these cells produce are essential for FDC development.

Animals↗
PubMed1993

Follicular dendritic cells and B cell costimulation.

Ag-bearing follicular dendritic cells (FDC) are found throughout secondary lymphoid tissues in close association with rapidly proliferating germinal center B lymphocytes. We reasoned that FDC might provide costimulatory signals that would enhance the ability of Ag to stimulate B cell proliferation in the germinal centers. To test this, FDC were cultured with B cells activated by a slg-dependent (goat anti-mouse mu conjugated to dextran (anti-mu-dex)) or -independent (LPS) pathway and their proliferation was measured by using [3H]thymidine incorporation. The addition of FDC markedly augmented B cell proliferation in a dose-dependent fashion. Depletion of FDC from cultures abrogated the increased proliferation. Addition of highly purified FDC obtained from cell sorting resulted in B cell costimulation, whereas addition of other sorted cells was without effect. The FDC accessory activity was apparent over the entire culture period and over a wide range of either polyclonal B cell activator. When B cells and activators were cultured in the absence of FDC, only about one fourth of the cells remained viable after 3 days. In contrast, virtually all cells in cultures containing FDC, B cells, and activator were viable. Cultures containing FDC and B cells from nude mice proliferated normally in the presence of anti-mu-dex plus rIL-4, implying that IL-4 provides adequate T cell help in this system. The costimulatory activity of the FDC could not replace either the anti-mu-dex or IL-4 in this system and was not MHC restricted. These data support the concept that FDC not only provide Ag but also facilitate B cell proliferation by means of other costimulatory interactions that contribute to make the microenvironment in the germinal center favorable for B cells to proliferate.

Animals↗
PubMed1992

Murine follicular dendritic cells and low affinity Fc receptors for IgE (Fc epsilon RII).

The present study was undertaken to determine whether mouse follicular dendritic cells (FDC) bear Fc epsilon RII (CD23) and whether IgE-immune complexes are retained by FDC. Mouse Fc epsilon RII was localized by both L and electron microscopy using the mAb B3B4. In lymph nodes of normal mice, Fc epsilon RII was low but detectable on FDC. By 14 days after Nippostrongylus brasiliensis infection, the level of Fc epsilon RII increased on B lymphocytes located in the cortex of draining mesenteric lymph nodes. However, the Fc epsilon RII level on FDC remained low. Although numerous IgE-producing plasma cells were seen at day 14, very little IgE was associated with FDC. By 26 days after infection, Fc epsilon RII was observed on FDC in increased levels and IgE binding was clearly associated with FDC. Unexpectedly, FDC of control mice immunized with albumin in CFA to elicit an IgG response showed intense labeling for Fc epsilon RII. In contrast, the B cells exhibited very little Fc epsilon RII. IgE immune complexes were observed in association with FDC in the CFA-immunized mice. When mice were given a hapten-specific monoclonal of the IgE isotype, hapten carrier complexes were trapped and retained on Fc epsilon RII-bearing FDC. In conclusion, FDC were clearly one of the major murine cell types bearing Fc epsilon RII. IgE immune complexes were found in association with FDC and Fc epsilon RII appeared to play a major role in trapping and retaining IgE immune complexes. FDC Fc epsilon RII was subject to regulatory control, but the Fc epsilon RII level on FDC was regulated very differently from the Fc epsilon RII level on B cells.

Animals↗
PubMed1992

Brain levels of polyethylene glycol-conjugated superoxide dismutase following fluid percussion brain injury in rats.

Polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) is being explored as an agent to reduce oxygen radical-mediated damage following brain injury. Yet little is known concerning the site of action of IV-administered PEG-SOD or the capacity of this conjugated enzyme to enter the brain. The purpose of this study was to determine the brain content of PEG-SOD in normal and fluid percussion injured rats. The fluid percussion device was attached over the right parietal cortex and a moderate (2.0 atm) intensity injury was produced. PEG-SOD was conjugated with 125I and given (2000 U/kg, 5 microCi/kg) to rats either 30 min before or 30 min after brain injury. Another group received [125I]PEG-SOD but was not injured. Plasma and left and right brain hemispheres were counted for [125I]PEG-SOD. Plasma levels of [125I]PEG-SOD declined similarly in all three groups during the 90-min period after IV administration. Brain [125I]PEG-SOD was low in control animals (0.034 U/g wet wt). In animals given PEG-SOD after injury the brain level was elevated sixfold in both the left and right hemispheres, compared to control. In rats given the drug before injury, [125I]PEG-SOD was 10 times control level in the right hemisphere, which is the side on which the injury device is attached, and 6 times control level in the left hemisphere. We conclude that traumatic brain injury produces an increase in brain PEG-SOD. The exact cellular site of the increased brain PEG-SOD remains to be clarified.

Animals↗
PubMed1992

Brain and tissue distribution of polyethylene glycol-conjugated superoxide dismutase in rats.

BACKGROUND AND PURPOSE: The purpose of this study was to determine the distribution of polyethylene glycol-conjugated superoxide dismutase in the brain, cerebrospinal fluid, and various organs. METHODS: Distribution of iodine-125-labeled polyethylene glycol-conjugated superoxide dismutase was determined in three groups of male Sprague-Dawley rats: a normotensive sham control group (n = 9) and groups given 125I-labeled polyethylene glycol-conjugated superoxide dismutase either 30 minutes before (n = 10) or 30 minutes after (n = 7) norepinephrine-induced hypertensive injury. RESULTS: In the first 30 minutes after intravenous administration, polyethylene glycol-conjugated superoxide dismutase plasma activity declined to 70% of the initial value and then decreased negligibly between 30 and 90 minutes. Levels of 125I-labeled polyethylene glycol-conjugated superoxide dismutase in normotensive animals were low in the brain and cerebrospinal fluid and highest in kidney. Brain levels of polyethylene glycol-conjugated superoxide dismutase were elevated only in those rats that received it before hypertensive injury; however, cerebrospinal fluid levels were elevated in animals receiving the drug either before or after hypertensive injury. CONCLUSION: Our results suggest that the blood-brain barrier becomes more permeable to polyethylene glycol-conjugated superoxide dismutase only during the hypertensive period but that the blood-cerebrospinal fluid barrier sustains more permanent injury. We suggest that the therapeutic effectiveness of polyethylene glycol-conjugated superoxide dismutase in hypertensive brain injury is due to its action in the vascular wall or to its extracellular activity in the cerebrospinal fluid.

Animals↗
PubMed1991

Iccosomes and the secondary antibody response.

Iccosomes derived from follicular dendritic cells (FDC) are believed to play an important role in dispersion of antigen necessary for induction of anamnestic responses. Because FDC are aberrant and iccosome release has not been observed in aged mice, we hypothesized that these animals would be impaired in their ability to mount anamnestic responses. To test this, anamnestic responses were compared in aged and control mice. To ensure the presence of functional lymphocytes, some aged mice were reconstituted with T- and B-memory cells obtained from control mice. Anamnestic responses in aged mice were markedly depressed even when given functional memory cells. To more directly relate the impaired antibody response of aged mice to FDC function, antigen-bearing FDC from either aged or control mice were incubated with T- and B-memory cells from control mice to induce an anamnestic response. Antigen retained by FDC from aged mice was much less immunogenic than antigen retained by FDC from control mice. Since iccosome formation does not appear in aged mice, iccosome-like fragments were generated by sonicating FDC from aged mice and tested for their ability to induce an anamnestic response. This procedure restored the ability of antigen retained on FDC from aged mice to induce a normal anamnestic response. These data support the concept that the inability to form and disperse iccosomes contributes to the impaired ability of aged mice to mount anamnestic antibody responses and provides further support for the role of iccosomes in anamnestic responses.

Aging↗
PubMed1990

Kinetics of germinal center development in lymph nodes of young and aging immune mice.

Recent findings imply that germinal center paucity in old mice, at least in part, results from a defect in the mechanisms responsible for the transport of antigens to lymphoid nodules (follicles) and the consequent impairment of the antigen retaining reticulum (ARR) of follicular dendritic cells (FDCs). The present objective was to observe the kinetics of lymph node germinal center development in old mice having antigen transport and ARR deficits. Germinal center development was monitored in popliteal (PLN) and axillary (AXLN) lymph nodes of 6-8 wk and 23-mo-old horseradish peroxidase (HRP) immune C57BL/6 mice. Using the selective binding of germinal center B cells for peanut agglutinin (PNA), germinal centers were identified in serial vibratome sections following histochemical labeling with PNA-peroxidase conjugates at times 0, 15 min, 1, 3, 5, and 10 days after footpad challenge with 8 micrograms HRP. To follow the fate of preexisting (environmental antigen-induced) germinal centers and the development of de novo (HRP-induced) germinal centers, it was essential to distinguish between these germinal centers. Accordingly, PNA positive germinal centers associated with HRP-retaining (peroxidase positive) ARR were identified as de novo germinal centers and germinal centers not associated with a peroxidase positive ARR were classified as preexisting germinal centers. Kinetic analysis of PNA positive germinal centers showed the following: 1) Preexisting, environmentally-induced germinal centers dissociated and disappeared by day 3 as indicated by a decline in their numbers after antigen injection: the process of germinal center dissociation remained unaffected by aging. 2) The latency of de novo germinal center appearance was approximately equal in duration (approximately 3 days) to the disappearance of pre-existing germinal centers. 3) The number and size of de novo HRP-induced germinal centers increased through the experimental period in young lymph nodes, but in old mice these parameters were depressed, resulting in a significant germinal center deficit. 4) The ratio of HRP-retaining ARR to de novo induced germinal centers was 1:1 in young and responder old mice. This ratio was not affected by aging. This finding favored the concept that antigen retention in ARR is a requirement of germinal center development. The observations supported our hypothesis that germinal center development, at least in part, depends on a normal antigen transport by showing that in aged mice with defective antigen transport-related ARR and iccosome deficits there is an impaired development of germinal centers.

Aging↗
PubMed1989

Antibody-forming cell induction during an early phase of germinal centre development and its delay with ageing.

The present study was initiated to determine if an early phase of germinal centre (GC) development is associated with the generation of antibody-forming cells (AFC). Germinal centres in draining lymph nodes from immune mice were examined histochemically after secondary immunization for the presence of AFC at both the light and electron microscopic levels. Additionally, peanut agglutinin (PNA) high (Hi) GC B cells were isolated, placed in cell culture and specific antibody production was monitored at successive intervals. Electron microscopy showed that plasma cells in all stages of differentiation were present within GC at 3-5 days and to a lesser extent at 7 days following antigenic challenge. Furthermore, PNAHi GC B cells obtained between Days 3 and 5 spontaneously produced specific IgG when placed in culture. Germinal centre B cells isolated either before or after this period did not produce antibody without the addition of T-cell cytokines. Induction of AFC in GC occurred at the time when GC B cells acquire follicular dendritic cell (FDC)-derived, immune complex-coated bodies (iccosomes) and process and present this antigen to helper T cells. This suggested a causal relationship between iccosome release and AFC induction. Support for this was obtained by examination of AFC induction in aged mice where iccosome release has not been observed. Peanut agglutinin-positive GC B cells isolated from aged mice on Days 3-5 after antigen challenge failed to spontaneously produce specific antibody. Collectively, these data show that GC development 3-5 days after booster immunization results in AFC generation and suggests a role for FDC iccosomes in their induction.

Aging↗
PubMed1988

A subpopulation of germinal center B cells differentiate directly into antibody forming cells upon secondary immunization.

In the present study we sought to test the hypothesis that GC B cells may be stimulated to differentiate into AFCs during the induction of the secondary antibody response. To test this we gave HRP immune mice a booster immunization and looked for AFCs in the GCs making anti-HRP specific antibody. Within 3 days cells in the GCs were making anti-HRP. Most of the cells were just starting to make immunoglobulin in the rough endoplasmic reticulum but some were nearly mature plasma cells like those in the medullary cords. Furthermore, we isolated GC B cells after a boost with OVA and tested their ability to differentiate directly into AFCs. Data obtained using an OVA specific RIA indicated that purified GC B cells would differentiate and produce specific antibody in the absence of added T cells or antigen. Examination of the cells after 5 days in culture indicated that many of them had differentiated into large plasma cells. These results obtained both in vivo and in vitro demonstrate that shortly after booster immunization GC B cells receive the appropriate antigen and T cell signals in vivo to differentiate and become AFCs.

Animals↗