RESUMO
BACKGROUND: Previous immunohistochemical studies of muscle from patients with inclusion body myositis and polymyositis found many more T cells than B cells, suggesting a role for intramuscular cell-mediated immune mechanisms rather than humoral mechanisms. METHODS: Microarray studies were performed on muscle biopsy specimens from 40 patients with inclusion body myositis (IBM; n = 23), polymyositis (PM; n = 6), and without neuromuscular disease (n = 11). Reverse transcription PCR of selected immunoglobulin gene transcripts was performed on two patient samples. Qualitative immunohistochemical studies for B-cell lineage cell surface markers were performed on 28 muscle specimens and quantitative studies performed on a subset of 19 untreated patients with IBM or PM. CD138+ cells were isolated from muscle using laser capture microdissection, and immunoglobulin transcripts were PCR amplified to determine the presence or absence of immunoglobulin gene rearrangements unique to the B-cell lineage. RESULTS: Immunoglobulin gene transcripts accounted for 59% in IBM and 33% in PM of the most stringently defined highest differentially expressed muscle transcripts compared with normal. Plasma cells, terminally differentiated B cells expressing CD138 but not CD19 or CD20, are present in IBM and PM muscle in numbers several times higher than B cells. CONCLUSIONS: There are differentiated B cells in the form of CD138+ plasma cells within the muscle of patients with inclusion body myositis and polymyositis. The principle of linked recognition of B-cell activation predicts several strategies for autoantigen discovery that could not otherwise be pursued through the study of the infiltrating T-cell population alone.
Assuntos
Músculo Esquelético/imunologia , Músculo Esquelético/patologia , Miosite de Corpos de Inclusão/diagnóstico , Miosite de Corpos de Inclusão/imunologia , Plasmócitos/imunologia , Polimiosite/diagnóstico , Polimiosite/imunologia , Antígenos de Superfície/genética , Antígenos de Superfície/imunologia , Autoantígenos/genética , Autoantígenos/imunologia , Linfócitos B/imunologia , Biomarcadores/metabolismo , Biópsia , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Linhagem da Célula/genética , Linhagem da Célula/imunologia , Humanos , Imunoglobulinas/genética , Imunoglobulinas/imunologia , Imuno-Histoquímica , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/imunologia , Músculo Esquelético/fisiopatologia , Miosite de Corpos de Inclusão/fisiopatologia , Plasmócitos/patologia , Polimiosite/fisiopatologia , Proteoglicanas/genética , Proteoglicanas/imunologia , RNA Mensageiro/análise , RNA Mensageiro/genética , Sindecana-1 , Sindecanas , Linfócitos T/imunologia , Linfócitos T/patologiaRESUMO
The effectiveness of basic fibroblast growth factor and nerve growth factor in preventing the lesion-induced disappearance of septal cholinergic neurons was compared by using a computerized data-acquisition system and a digital brain atlas that yielded quantitative and distributional information. Adult rats were given unilateral partial transections of the fimbria and then received daily intraventricular injection of one of the growth factors for 15 days. Given the high degree of co-localization of nerve growth factor receptors with choline acetyltransferase in these areas, cholinergic neurons were identified by nerve growth factor receptor immunoreactivity. Their locations were plotted in the context of a three-dimensional brain atlas permitting the analysis of relative distributions of cholinergic neurons in control brains and those of animals treated with each growth factor. The cholinergic cell disappearance induced by the partial fimbrial transection was restricted to the medial septal nucleus and the vertical limb of the diagonal band of Broca. Within the affected areas cholinergic cell disappearance increased gradually in severity from anterior to posterior levels of the septal nucleus. Both growth factors prevented the disappearance of cholinergic cell bodies in medial septal nucleus and vertical limb of the diagonal band. In lesioned control animals the unilateral cell disappearance amounted to 53.5% of the number of cholinergic neurons of the unlesioned side. Nerve growth factor and basic fibroblast growth factor reduced this disappearance to 13% and 28%, respectively. The distribution of cholinergic cells was the same in animal treated with each growth factor, suggesting that the two growth factors protect the same population of cholinergic neurons.
Assuntos
Mapeamento Encefálico , Encéfalo/fisiologia , Ventrículos Cerebrais/fisiologia , Colina O-Acetiltransferase/metabolismo , Fator 2 de Crescimento de Fibroblastos/farmacologia , Fatores de Crescimento Neural/farmacologia , Neurônios/fisiologia , Receptores de Superfície Celular/fisiologia , Encéfalo/efeitos dos fármacos , Ventrículos Cerebrais/efeitos dos fármacos , Grupo dos Citocromos c/metabolismo , Fator 2 de Crescimento de Fibroblastos/administração & dosagem , Injeções Intraventriculares , Fatores de Crescimento Neural/administração & dosagem , Neurônios/efeitos dos fármacos , Receptores de Superfície Celular/efeitos dos fármacos , Receptores de Fatores de Crescimento de Fibroblastos , Receptores de Fator de Crescimento NeuralRESUMO
Quantitative morphometric methods were used in mice to study the effect postnatal olfactory deprivation has on tufted cell size and number. The two layers containing tufted cells, the external plexiform and glomerular layers, are considerably smaller in the deprived olfactory bulbs than in the contralateral, experienced olfactory bulbs. While most of this volumetric deficit may be due to an attenuation of synaptogenesis and dendritic elaboration, an additional factor contributing to the reduced volume of these bulbar layers is a substantial loss of tufted cells. Since tufted cells are generated prenatally, their reduced number in the postnatally deprived olfactory bulb is probably a consequence of retarded migration or cell death.
Assuntos
Animais Recém-Nascidos/fisiologia , Contagem de Células , Bulbo Olfatório/citologia , Privação Sensorial/fisiologia , Animais , Movimento Celular , Sobrevivência Celular , Camundongos , Camundongos Endogâmicos ICR , Neurônios/fisiologia , Bulbo Olfatório/fisiologiaRESUMO
Quantitative morphometric methods were used to examine the effects of early unilateral anosmia on two classes of granule cells in developing mouse olfactory bulbs. Volumetric results show that the internal granule cell layer in the deprived olfactory bulb is significantly smaller than the same layer in the experienced olfactory bulb. The major factor contributing to this retarded development is a selective loss of one class of interneurons; dark granule cell number is substantially reduced, while light granule cell number is not. This selective effect appears to be related to the time course of cell proliferation and differentiation and provides clues to the way early experience regulates neural development.