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At least 163 records · Page 9
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Systems biology predicts that fibrosis in tuberculous granulomas may arise through macrophage-to-myofibroblast transformation

Mycobacterium tuberculosis (Mtb) infection causes tuberculosis (TB), a disease characterized by development of granulomas. Granulomas consist of activated immune cells that cluster together to limit bacterial growth and restrict dissemination. Control of the TB epidemic has been limited by lengthy drug regimens, antibiotic resistance, and lack of a robustly efficacious vaccine. Fibrosis commonly occurs during treatment and is associated with both positive and negative disease outcomes in TB but little is known about the processes that initiate fibrosis in granulomas. Human and nonhuman primate granulomas undergoing fibrosis can have spindle-shaped macrophages with fibroblast-like morphologies suggesting a relationship between macrophages, fibroblasts, and granuloma fibrosis. This relationship has been difficult to investigate because of the limited availability of human pathology samples, the time scale involved in human TB, and overlap between fibroblast and myeloid cell markers in tissues. To better understand the origins of fibrosis in TB, we used a computational model of TB granuloma biology to identify factors that drive fibrosis over the course of local disease progression. We validated the model with granulomas from nonhuman primates to delineate myeloid cells and lung-resident fibroblasts. Our results suggest that peripheral granuloma fibrosis, which is commonly observed, can arise through macrophage-to-myofibroblast transformation (MMT). Further, we hypothesize that MMT is induced in M1 macrophages through a sequential combination of inflammatory and anti-inflammatory signaling in granuloma macrophages. We predict that MMT may be a mechanism underlying granuloma-associated fibrosis and warrants further investigation into myeloid cells as drivers of fibrotic disease.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

53BP1 Repair Kinetics for Prediction of In Vivo Radiation Susceptibility in 15 Mouse Strains

We present a novel mathematical formalism to predict the kinetics of DNA damage repair after exposure to both low- and high-LET radiation (X rays; 350 MeV/n 40 Ar; 600 MeV/n 56 Fe). Our method is based on monitoring DNA damage repair protein 53BP1 that forms radiation-induced foci (RIF) at locations of DNA double-strand breaks (DSB) in the nucleus and comparing its expression in primary skin fibroblasts isolated from 15 mice strains. We previously reported strong evidence for clustering of nearby DSB into single repair units as opposed to the classic "contact-first" model where DSB are considered immobile. Here we apply this clustering model to evaluate the number of remaining RIF over time. We also show that the newly introduced kinetic metrics can be used as surrogate biomarkers for in vivo radiation toxicity, with potential applications in radiotherapy and human space exploration. In particular, we observed an association between the characteristic time constant of RIF repair measured in vitro and survival levels of immune cells collected from irradiated mice. Moreover, the speed of DNA damage repair correlated not only with radiation-induced cellular survival in vivo, but also with spontaneous cancer incidence data collected from the Mouse Tumor Biology database, suggesting a relationship between the efficiency of DSB repair after irradiation and cancer risk.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
DOE OSTI2024

Comparison of Intact Fish Skin Graft and Allograft as Temporary Coverage for Full-Thickness Burns: A Non-Inferiority Study

The extent and depth of burn injury may mandate temporary use of cadaver skin (allograft) to protect the wound and allow the formation of granulation tissue while split-thickness skin grafts (STSGs) are serially harvested from the same donor areas. However, allografts are not always available and have a high cost, hence the interest in identifying more economical, readily available products that serve the same function. This study evaluated intact fish skin graft (IFSG) as a temporary cover to prepare the wound bed for STSG application. Thirty-six full-thickness (FT) 5 × 5 cm burn wounds were created on the dorsum of six anesthetized Yorkshire pigs on day -1. To mimic the two-stage clinical situation, on day 0, wounds were excised down to a bleeding wound bed and a temporary cover (either IFSG or cadaver porcine skin) was applied; then, on day 7, wounds were debrided to a viable wound bed prior to the application of autologous 1.5:1 meshed STSG (mSTSG). Rechecks were performed on days 14, 21, 28, 45, and 60 with digital images, non-invasive measurements, and punch biopsies. The IFSG created a granulated wound bed receptive to the application of an mSTSG. FT burn wounds treated with an IFSG had similar outcome measures, including contraction rates, trans-epidermal water loss (TEWL) measurements, hydration, and blood perfusion levels, compared to cadaver skin-treated burn wounds. Pathology scoring indicated significant differences between the allograft- and IFSG-treated wounds on day 7, with the IFSG having increased angiogenesis, granulation tissue formation, and immune cells. Pathology scoring indicated no significant differences once mSTSGs were applied to wounds. The IFSG performed as well as cadaver skin as a temporary cover and was not inferior to the standard of care, suggesting the potential to transition IFSGs into clinical use for burns.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Sclerostin Depletion Induces Inflammation in the Bone Marrow of Mice

Romosozumab, a humanized monoclonal antibody specific for sclerostin (SOST), has been approved for treatment of postmenopausal women with osteoporosis at a high risk for fracture. Previous work in sclerostin global knockout (Sost-/- ) mice indicated alterations in immune cell development in the bone marrow (BM), which could be a possible side effect in romosozumab-treated patients. Here, we examined the effects of short-term sclerostin depletion in the BM on hematopoiesis in young mice receiving sclerostin antibody (Scl-Ab) treatment for 6 weeks, and the effects of long-term Sost deficiency on wild-type (WT) long-term hematopoietic stem cells transplanted into older cohorts of Sost-/- mice. Our analyses revealed an increased frequency of granulocytes in the BM of Scl-Ab-treated mice and WT→Sost -/- chimeras, indicating myeloid-biased differentiation in Sost-deficient BM microenvironments. This myeloid bias extended to extramedullary hematopoiesis in the spleen and was correlated with an increase in inflammatory cytokines TNFα, IL-1α, and MCP-1 in Sost-/- BM serum. Additionally, we observed alterations in erythrocyte differentiation in the BM and spleen of Sost-/- mice. Taken together, our current study indicates novel roles for Sost in the regulation of myelopoiesis and control of inflammation in the BM.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1995

Portable Immune-Assessment System

Portable immune-assessment system developed for use in rapidly identifying infections or contaminated environment. System combines few specific fluorescent reagents for identifying immune-cell dysfunction, toxic substances, buildup of microbial antigens or microbial growth, and potential identification of pathogenic microorganisms using fluorescent microplate reader linked to laptop computer. By using few specific dyes for cell metabolism, DNA/RNA conjugation, specific enzyme activity, or cell constituents, one makes immediate, onsite determination of person's health or of contamination of environment.

Pierson, Duane L.↗
NASA NTRS1999

Development of a Whole Blood Staining Device for use During Space Shuttle Flights

Exposure to microgravity during space flight results in profound physiologic changes. Numerous studies have shown changes in circulating populations of peripheral blood immune cells immediately after space flight. It is currently unknown if these changes result from exposure to microgravity or are caused by the stress of reentry and readaptation to gravity. We have developed the whole blood staining device as a system for the staining of whole blood collected during space flight for subsequent flow cytometric analysis, This device contains all liquids to address safety issues concerned with space flight and also moves the cells through the staining, lyse/fixation and dilution steps.

Sams, Clarence F.↗
NASA NTRS2001

Elevated stress hormone levels relate to Epstein-Barr virus reactivation in astronauts

OBJECTIVE: The objective of this study was to determine the effects of stress and spaceflight on levels of neuroendocrine hormones and Epstein-Barr virus (EBV)-specific antibodies in astronauts. METHODS: Antiviral antibody titers and stress hormones were measured in plasma samples collected from 28 astronauts at their annual medical exam (baseline), 10 days before launch (L-10), landing day (R+0), and 3 days after landing (R+3). Urinary stress hormones were also measured at L-10 and R+0. RESULTS: Significant increases (p <.01) in EBV virus capsid antigen antibodies were found at all three time points (L-10, R+0, and R+3) as compared with baseline samples. Anti-EBV nuclear antigen antibodies were significantly decreased at L-10 (p <.05) and continued to decrease after spaceflight (R+0 and R+3, p <.01). No changes were found in antibodies to the nonlatent measles virus. The 11 astronauts who showed evidence of EBV reactivation had significant increases in urinary epinephrine and norepinephrine as compared with astronauts without EBV reactivation. CONCLUSION: These findings indicate that physical and psychological stresses associated with spaceflight resulted in decreased virus-specific T-cell immunity and reactivation of EBV.

NASA Center JSC↗
NASA NTRS2001

Peripheral leukocyte subpopulations and catecholamine levels in astronauts as a function of mission duration

OBJECTIVE: The objective of this study was to determine the effects of spaceflight duration on immune cells and their relationship to catecholamine levels. METHODS: Eleven astronauts who flew aboard five different US Space Shuttle flights ranging in duration from 4 to 16 days were studied before launch and after landing. RESULTS: Consistent with prior studies, spaceflight was associated with a significant increase in the number of circulating white blood cells (p <.01), including neutrophils (p <.01), monocytes (p <.05), CD3+CD4+ T-helper cells (p <.05), and CD19+ B cells (p <.01). In contrast, the number of CD3-CD16+56+ natural killer cells was decreased (p <.01). Plasma norepinephrine levels were increased at landing (p <.01) and were significantly correlated with the number of white blood cells (p <.01), neutrophils (p <.01), monocytes (p <.01), and B cells (p <.01). Astronauts who were in space for approximately 1 week showed a significantly larger increase on landing in plasma norepinephrine (p =.02) and epinephrine (p =.03) levels, as well as number of circulating CD3+CD4+ T-helper cells (p <.05) and CD3+CD8+ T-cytotoxic cells (p <.05) as compared with astronauts in space for approximately 2 weeks. CONCLUSIONS: The data suggest that the stress of spaceflight and landing may lead to a sympathetic nervous system-mediated redistribution of circulating leukocytes, an effect potentially attenuated after longer missions.

Flight Experiment↗
NASA NTRS1999

The use of a spaceflight-compatible device to perform WBC surface marker staining and whole-blood mitogenic activation for cytokine detection by flow cytometry

Significant changes have recently been described regarding circulating peripheral immune cells immediately following spaceflight. Existing methods for immunophenotype staining of peripheral blood in terrestrial labs do not meet the constraints for flight on the Space Shuttle. We have recently described the development and use of the Whole Blood Staining Device (WBSD), a simple device for staining flow cytometry specimens during spaceflight. When preparing samples with the WBSD, all liquids are safely contained as the cells are moved through staining, lysis and fixation steps. Here we briefly review the use of the WBSD, and then describe another versatile adaptation, a modification to perform intracellular staining of cytokines for detection by flow cytometry. Alterations in cytokine production have been reported both in ground-based simulated microgravity culture and in astronaut samples returning from spaceflight. Data regarding microgravity effects on cytokine production for specific subpopulations of cells is lacking. Flow cytometric cytokine analysis offers the unique ability to perform simultaneous surface marker analysis and positively identity cytokine producing subsets of cells. The utilization of the WBSD provides the ability to perform rapid and routine mitogenic activation during spaceflight coupled with the ability to perform simultaneous surface marker analysis. The only external requirements for this procedure are an in-flight 37-degree incubator and the capacity for 4-degree storage.

NASA Discipline Regulatory Physiology↗
NASA NTRS2019

Predicting Cancer Risk from Ionizing Radiation

The ability to predict cancer risk associated with exposure to low doses of high-LET ionizing radiation (IR) remains a challenge. Epidemiological methods lack the sensitivity and power to provide detailed risk estimates for cancer and ignore individual variance in IR sensitivity. We have hypothesized that DNA repair capacity can be used as a marker to evaluate and differentiate individual radiation sensitivity. More specifically, this work is based on the concept that the combined time-dose dependence of radiation-induced foci (RIF) of p53-binding protein 1 (53BP1) following low-LET exposure contains sufficient information to infer sensitivity to any other LET. Our hypothesis was tested in 15 different mouse strains as well as in primary human immune cells. We first approached individual ionizing radiation sensitivity in a mouse model by culturing primary skin fibroblasts extracted from 76 mice of 15 different genetic backgrounds and exposing them to HZE particles and X-rays. This work is one of the most extensive studies on the kinetics and possible genetic underpinnings of radiation-induced DNA damage and repair. Our results is in agreement with a DNA repair model we previously postulated, where nearby DNA double strand breaks (DSB) in the nucleus are brought together for more efficient repair, leading to RIF clustering. Such mechanism was evidenced by a specific dose and LET dependence of RIF numbers. Briefly, RIF quantification after low-LET X-ray exposure showed an asymptotic saturation for doses between 1 Gy and 4 Gy 4 hours post-irradiation across all 15 strains. The clustering of DSB across all strains also led to more RIF/Gy for lower LET (X-ray and 350 MeV/n Ar) than for higher LET (600 MeV/n Fe) 4 hours post-exposure. Considering the fact that the number of DSB/Gy should be independent of LET, our data suggest there are more DSB in individual RIF as the LET increases. RIF numbers for 24 and 48 hours post-exposure led to the inverse trend, with more remaining RIF/Gy for higher LET (by 600 MeV/n Fe). This result suggests cells have more difficulty resolving RIF from higher LET as they the number DSB/RIF increases. Note that for most conditions, the variance of RIF/Gy was small within individual animals of the same strain and large between strains, suggesting a strong genetics component. Furthermore, we present our preliminary data from an ongoing study on human genetic associations with IR sensitivity. To address the human variability in responses to HZE particle irradiation in a maximally comprehensive manner, we are in the process of collecting and isolating primary blood mononuclear cells from 768 healthy subjects of European descent, 18-75 years of age, 50/50 male/female distribution. We have analyzed 53BP1+ RIF formation as well as oxidative stress and cell death in primary cells from 192 subjects in response to the same HZE particles as used in mice: 600 MeV/n Fe, 350 MeV/n Ar and 350 MeV/n Si, 1.1 and 3 particles/100m2, 4 and 24 hours after irradiation. We will next complete the quantification of HZE particle-induced DNA and cellular damage in the remaining subjects and compare it to their responses to low-LET irradiation. Finally, we will perform GWAS analysis to identify human genomic associations with IR sensitivity and potential targets for biomarker development.

High-LET radiation↗
NASA NTRS2018

MPLA as an Innovative Immune Countermeasure

Spaceflight perturbs the human immune system. Among other manifestations, crewmembers may experience latent herpes viruses reactivation due to impaired lymphocyte function, as well as allergic/hypersensitivity reactions. Considering future space travel will be of longer duration (thereby increasing stress, exposure to radiation, etc…) with no rapid return option, it is of paramount importance to develop a countermeasure(s) to immune dysregulation. Monophosphoryl lipid A (MPLA) is a derivative of lipopolysaccharide (LPS), a potent inflammatory agent that can cause septic shock. MPLA possesses the immune-stimulatory effects of LPS without the adverse inflammatory effects. We hypothesize that treating immune cells with MPLA will boost their function enough to overcome the inhibitory effects of microgravity. While MPLA has been tested as an adjuvant extensively in mice and preliminarily for human vaccines, it has never been assessed for efficacy in microgravity.

Makedonas, George↗
NASA NTRS2019

Characterization of Sensory and Shelter Enrichment in the Rodent Research Habitat

The ISS provides a platform for conducting Rodent Research (RR) in microgravity and 9 missions have been successfully conducted. The results from these experiments have begun to provide new insights into the effects of spaceflight on mammalian physiological systems. After RR-1-4, the Flight IACUC required inclusion of additional cage enrichment into the Rodent Habitats (RH) to "enhance animal well-being by providing animals with sensory and motor stimulation, through structures and resources that facilitate the expression of species typical behaviors". A Hut, in the form of a rigid, mesh igloo-like shelter was implemented beginning with RR-5. The potential influence of the Hut in the novel cage environment of RH on various spaceflight-sensitive physiological systems has not been fully explored. To understand the effects of the Hut, mice (female C57Bl/6J, 15wks) were housed in Vivarium cage (n=5), RH with Hut (n=5), No Hut (n=5), Nestlet (n=10), and Cocoon (n=10) for 7 weeks. There were no differences in weekly body mass or food consumption. Tail blood draw indicated no differences in plasma corticosterone levels, immune cell types, or IgA levels. 24hrs prior to euthanasia, Open Field (OF) and Novel Object (NO) tests were performed. There were no differences across groups, all mice engaged in thigmotaxis (arena wall proximity) in the OF over 50% of the recorded time, and thigmotaxis declined when a NO was introduced. Additional behavioral analysis from daily videos are in progress to quantify activity levels. Post-euthanasia, there were no differences in soleus muscle or adrenal gland mass. Analysis of distal femur cancellous revealed some differences in microarchitecture. These results show that introduction of the Hut may diminish differences observed between spaceflight and ground controls, warranting improved validation of Hut effects in space, and also underscore the value of thorough preflight, ground based testing.

Shirazi-Fard, Yasaman↗
NASA NTRSDate not supplied

Developing Open-Source Training Materials for AI/ML and Space Biological Sciences Using NASA Cloud-Based Data

Artificial Intelligence (AI) and Machine Learning (ML) has gained significant traction in the biological and biomedical research fields in the last two decades, in part thanks to an increasing culture of open data sharing and reuse. Due to its capability for identifying complex relationships and patterns, AI/ML methodology is particularly well suited to recognize and predict biological patterns from high-dimensional next-generation sequencing data (e.g. whole genome sequencing, transcriptomic sequencing), as well as from biological or medical imaging data (e.g. microscopy, computed tomography, ultrasound, magnetic resonance imaging, radiography). These methodologies hold particular promise for space biosciences research and automated space health monitoring systems. However, there are many key considerations for properly training, validating, and testing a machine learning model in biological research or clinical application. Even with the positive culture of Open Science and data sharing, inexperienced researchers working quickly without proper checks can produce models that perform poorly outside of the immediate training dataset. Lessons learned from biological AI/ML research indicate that Open Science principles such as data sharing and open-source code must go hand-in-hand with publicly available, high-quality training curricula in best practices, with modules centered on real-life scientific use cases and data so future AI/ML practitioners gain experience on real problems. Here we present the development of open-source training materials for AI/ML and space biosciences, as part of the NASA Transform to Open Science Training (TOPST) initiative. We develop 4 independent training programs, focused on the following topics: 1) Fundamentals of Machine Learning and Space Biosciences Domain, 2) Open Science, Artificial Intelligence, and Ethical Best Practices for Data Sharing and Analysis, 3) Using AI/ML Classification to Identify Gene Networks Affected By Space Exposure in Mouse Liver, and 4) Using Neural Networks to Find DNA Damage Patterns in Immune Cells after Radiation. All programs leverage cloud-based NASA biological datasets. The curriculum we present will enable worldwide access to training in AI/ML and scientific analysis.

James Andrew Casaletto↗
NASA NTRSDate not supplied

Creating Benchmark Data for Artificial Intelligence and Machine Learning Space Biology Research

To identify an appropriate AI/ML approach for a specific problem, the best practice is to measure algorithm performance through the benchmarking process. A scientific benchmark consists of an AI-ready dataset and a reference implementation on a specific scientific question. The NASA Science Mission Directorate (SMD) has started the “Benchmark Initiative for AI/ML to create scientific benchmark datasets in three applications: 1) scientific benchmarking, which finds the best algorithm for a specific problem; 2) application benchmarking, which measures algorithm performance against a set of parameters; and 3) system benchmarking, which evaluates performance of hardware and software architecture. Currently, there are no standardized datasets available to benchmark AI/ML algorithms in the domain of space biology. In this work, we constructed two AI/ML-ready biological datasets from experiments in space-flown mice: cellular imaging and RNA-seq. First, radiation-exposed immune cells harbor DNA damage foci that can be fluorescently marked to visualize the amount of damage following exposure to ionizing radiation. However, such large datasets are difficult to analyze visually, due to imaging inconsistencies and human bias, and classical image processing approaches can fail on imaging artifacts. AI/ML are therefore exciting alternative, providing the speed of machines and the accuracy of humans. We have made this dataset available at https://registry.opendata.aws/bps_microscopy/. Second, high-throughput nucleic acid sequencing (DNA-seq, RNA-seq) has become widespread in biomedical research due to the growing availability and affordability of these assays. However, most sequencing datasets suffer from high dimensionality and low sample count. In this work, we used a generative adversarial network to synthesize a standardized, AI-ready, publicly available benchmark dataset for space biology RNA-seq data with sufficient space-flown and ground control mouse liver samples from NASA GeneLab. This dataset is available at https://registry.opendata.aws/bps_rnaseq/. These datasets are now fully open the Space Biology community to test their favorite AI/ML approaches.

James Casaletto↗
NASA NTRSDate not supplied

Developing Open-Source Training Materials for AI/ML and Space Biological Sciences Using NASA Cloud-Based Data

Artificial Intelligence (AI) and Machine Learning (ML) has gained significant traction in the biological and biomedical research fields, in part due to a culture of open data sharing and reuse. AI/ML methodology is well-suited to recognize and predict biological patterns from high-dimensional next-generation sequencing data (e.g. whole genome sequencing, transcriptomic sequencing), as well as from biological or medical imaging data (e.g. microscopy, computed tomography, ultrasound, magnetic resonance imaging, radiography). These methodologies hold particular promise for space biosciences research and automated space health monitoring systems. However, there are key considerations for properly training, validating, and testing a machine learning model in biological research or clinical application. Inexperienced researchers can produce models that perform poorly outside of the training dataset. Open Science principles such as data sharing and open-source code must go hand-in-hand with publicly available, high-quality training curricula in best practices, with modules centered on real-life scientific use cases and data so future AI/ML practitioners gain experience on real problems. Here we present the development of open-source training materials for AI/ML and space biosciences, as part of the NASA Transform to Open Science Training (TOPST) initiative. We develop 4 independent training programs, focused on the following topics: 1) Fundamentals of Machine Learning and Space Biosciences Domain, 2) Open Science, Artificial Intelligence, and Ethical Best Practices for Data Sharing and Analysis, 3) Using AI/ML Classification to Identify Gene Networks Affected By Space Exposure in Mouse Liver, and 4) Using Neural Networks to Find DNA Damage Patterns in Immune Cells after Radiation. All programs leverage cloud-based NASA biological datasets. The curriculum we present will enable worldwide access to training in AI/ML and scientific analysis.

James Casaletto↗
NASA NTRS2001

Ongoing cell death and immune influences on regeneration in the vestibular sensory organs

Hair cells in the vestibular organs of birds have a relatively short life span. Mature hair cells appear to die spontaneously and are then quickly replaced by new hair cells that arise from the division of epithelial supporting cells. A similar regenerative mechanism also results in hair cell replacement after ototoxic damage. The cellular basis of hair cell turnover in the avian ear is not understood. We are investigating the signaling pathways that lead to hair cell death and the relationship between ongoing cell death and cell production. In addition, work from our lab and others has demonstrated that the avian inner ear contains a resident population of macrophages and that enhanced numbers of macrophages are recruited to sites of hair cells lesions. Those observations suggest that macrophages and their secretory products (cytokines) may be involved in hair cell regeneration. Consistent with that suggestion, we have found that treatment with the anti-inflammatory drug dexamethasone reduces regenerative cell proliferation in the avian ear, and that certain macrophage-secreted cytokines can influence the proliferation of vestibular supporting cells and the survival of statoacoustic neurons. Those results suggest a role for the immune system in the process of sensory regeneration in the inner ear.

Non-NASA Center↗
DOE OSTI2025

Fortifying the frontier: cell wall modifications during plant immunity

The plant cell wall (CW) was long thought to be a rigid barrier encasing the plant cell and protecting it against biotic and abiotic stressors. Different CW polysaccharides interact with each other, and modifications of either the components or organization of these polysaccharides result in impaired growth or immunity. Emerging evidence suggests that the CW is dynamically modified and reorganized based on internal and external cues. Thus, the CW is both the first barrier that pathogens encounter and the critical final step in defense signaling that leads to fortification of the CW. Here, in this work, we review recent findings on how CW components are remodeled to fortify the CW upon pathogen attack and propose a novel concept: layered CW remodeling as an immune strategy. Within this framework, we categorize three interconnected layers of CW remodeling upon pathogen attack: (i) rapid and reversible CW depositions that provide immediate but transient protection; (ii) flexible modifications with plausible signaling functions that integrate defense and surveillance; and (iii) irreversible fortifications that encase pathogen, delimiting infected cells from uninfected cells. This layered framework provides a cohesive view of how different CW modifications are integrated into, and contribute to, plant defense. We also discuss the challenges in studying CW modifications during biotic stresses and highlight important questions that remain unanswered.

Bhandari, Deepak D. [Michigan State Univ., East La↗
NASA NTRS1989

Presentation of antigen to T lymphocytes by non-immune B-cell hybridoma clones: evidence for specific and non-specific presentation

Non-immune SJL (H-2s) spleen cells were fused with non-secreting, non-antigen presenting (H-2d) Balb/c 653-myeloma cells and the hybridomas were cloned by two limiting dilutions. The resulting hybrid B-cell clones were tested for their antigen presentation capability to SJL T-cell lines that were specific for either lysozyme or myoglobin. In proliferative assays, 53% of the antigen presenting B-cell clones presented both myoglobin and lysozyme (general presenters) while the other 47% presented specifically either myoglobin or lysozyme (specific presenters). The ability to selectively present either myoglobin or lysozyme indicates that antigen presentation at the clonal level can be specific or non-specific depending on the particular B-cell clone.

B-Lymphocytes/immunology↗