Most polyreactive and antinuclear antibodies are removed from the human antibody repertoire during B cell development. To elucidate how B cell receptor (BCR) signaling may regulate human B cell tolerance, we tested the specificity of recombinant antibodies from single peripheral B cells isolated from patients suffering from X-linked agammaglobulinemia (XLA). These patients carry mutations in the Bruton's tyrosine kinase (BTK) gene that encode an essential BCR signaling component. We find that in the absence of Btk, peripheral B cells show a distinct antibody repertoire consistent with extensive secondary V(D)J recombination. Nevertheless, XLA B cells are enriched in autoreactive clones. Our results demonstrate that Btk is essential in regulating thresholds for human B cell tolerance.
Benign peripheral nerve sheath tumors such as schwannoma and neurofibroma have long been considered distinct entities. Recently, hybrid tumors demonstrating combined morphological features of neurofibroma and schwannoma have been described, primarily in dermal locations. Only 1 case of hybrid peripheral nerve sheath tumor of the orbit has been reported in the literature. Hybrid morphology is important to recognize because of its association with the neurofibromatoses, including schwannomatosis; however, the paucity of literature on orbital hybrid peripheral nerve sheath tumor poses a diagnostic challenge. This article describes a case of hybrid neruofibroma/schwannoma of the orbit arising from the supraorbital nerve with clinicopathologic correlation.
OBJECTIVEThe objective of this study was to investigate microstructural damage caused by pituitary macroadenomas by performing probabilistic tractography of the optic tracts and radiations using 7-T diffusion-weighted MRI (DWI). These imaging findings were correlated with neuro-ophthalmological results to assess the utility of ultra–high-field MRI for objective evaluation of damage to the anterior and posterior visual pathways.METHODSProbabilistic tractography employing 7-T DWI was used to reconstruct the optic tracts and radiations in 18 patients with adenomas and in 16 healthy volunteers. Optic chiasm compression was found in 66.7% of the patients and visual defects in 61.1%. Diffusion indices were calculated along the projections and correlated with tumor volumes and results from neuro-ophthalmological examinations. Primary visual cortical thicknesses were also assessed.RESULTSFractional anisotropy was reduced by 21.9% in the optic tracts (p < 0.001) and 17.7% in the optic radiations (p < 0.001) in patients with adenomas. Patients showed an 8.5% increase in mean diffusivity of optic radiations compared with healthy controls (p < 0.001). Primary visual cortical thickness was reduced in adenoma patients. Diffusion indices of the visual pathway showed significant correlations with neuro-ophthalmological examination findings.CONCLUSIONSImaging-based quantification of secondary neuronal damage from adenomas strongly correlated with neuro-ophthalmological findings. Diffusion characteristics enabled by ultra–high-field DWI may allow preoperative characterization of visual pathway damage in patients with chiasmatic compression and may inform prognosis for vision recoverability.
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