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The primary culture of marginal cells from the explant of the stria vascularis of guinea-pigs was established and confirmed by morphological, immunohistochemical and physiological characters of the cultivated cells. The positive stain of cytokeratin 18 without vimentin and desmin expressions indicated the epithelial origin of the cultured polygonal cells. Electron microscopical findings of cultured cells resembled the morphological characteristics of marginal cells. The addition of 100 μM ouabain to the cultured cells significantly increased the intracellular Na+ concentration, providing the evidence for the presence of Na+ pump. Using the cultured marginal cells identified by the above-mentioned findings, the effects of neurotransmitters and hormones in regulating intracellular Ca2+ concentration ([Ca2+]i) were investigated. The addition of 10−4 M ATP caused an increase in [Ca2+]i, which was independent of the presence of extracellular Ca2+. The rank order of agonist potency was ATP>α,β-methylene ATP>ADP. Adenosine, however, evoked no response. Cultured marginal cells may possessP2-purinergic receptors which mobilize Ca2+ from the intracellular Ca2+ pool. [Marginal cell, Cell culture, Na + K + ATPase, Intracellular Ca2+ concentration, ATP]

MRL/Mp-lpr/lpr (MRL/l) mice spontaneously develop autoimmune disease, characterized by glomerulonephritis, polyarteritis and polyarthritis. The lpr mice have defects in the Fas antigen, which plays a role in apoptosis, and it has been suggested that lack of negative selection of autoreactive T cells explains the initiation of the disease. The extremely high amount of autoantibodies may reflect additional immunoregulatory abnormalities. Antibody feedback regulation is an efficient way of up- or downregulating antibody responses. We have for the first time determined whether IgG-mediated suppression as well as IgM-mediated enhancement operates normally in these mice. MRL/l and MRL/Mp(-)+/+ (MRL/n) mice of different ages were therefore immunized with sheep erythrocyte (SRBC)-specific IgG or IgM antibodies followed by SRBC. Control groups received antigen alone. Five days later, the antigen-specific plaque-forming cell response was measured. IgG induced more than 90% suppression in both MRL/l and MRL/n in mice of all ages tested. This degree of suppression is in the same range as for other, normal mouse strains. In contrast, IgM-mediated enhancement was completely absent in 12-week-old MRL/l mice but normal in 8-week-old MRL/l as well as in MRL/n mice of all ages tested. When spleens and lymph nodes were immunohistochemically studied using a mAb specific for complement receptors 1 and 2 (CR1/CR2), an abnormal follicular structure was demonstrated in 12-week-old MRL/l mice. The antibody response of both 8- and 13-week-old MRL/l mice in vivo, after downregulation of these receptors, was inhibited by 85-96%. Thus, the presented data demonstrate that MRL/l mice with overt autoimmune disease are refractory to IgM-mediated enhancement of antigen-specific antibody production. We believe that this abnormal antibody feedback regulation is due to abnormal follicular structure in lymphoid organs of old MRL/l mice, hence the inability to localize and present antigen in a normal way.

IgA nephropathy (IgAN) is thought to be mediated by the glomerular deposition of circulating immune complexes containing IgA as the major antibody component. Tonsillitis often precedes IgAN, and tonsillectomy is an efficient treatment of IgAN. Thus, the tonsil may cause initial and/or progressive events leading to IgAN. To determine the pathological features of tonsillar lymphoid cells, we transferred tonsillar mononuclear cells from IgAN patients to SCID mice. Although human IgG-, IgM- and IgA-positive cells were detected in the spleens of SCID-Hu mice, they failed to reproduce the increase in serum IgA level and glomerular deposition. These results suggest that other factors are needed for the progression of IgAN.

Hearing acuity and inner ear disorders of MRL/ lpr mice, bred for the study of autoimmune disease, were examined in comparison to those of BALB/c mice. The auditory brain stem response threshold of 20-week-old MRL/ lpr mice was significantly higher than that of BALB/c mice of the same age (p < .01). The pathologic changes of 20-week-old MRL/ lpr mice were characterized by the degeneration of intermediate cells, widened intercellular spaces, and immunoglobulin G deposition on the basement membrane of strial blood vessels as well as in the basal infolding of strial marginal cells, which were absent in BALB/c mice. That there were no other evident pathologic findings in the cochlea or middle ear suggests that these changes in the stria vascularis seemed to be responsible for the sensorineural hearing loss of this mouse. The MRL/ lpr mouse was thought to be a good experimental model to study the spontaneous sensorineural hearing loss caused by an immune reaction.

食道原発・未分化小細胞癌の1例を報告する. 患者は49歳男性. 検診で食道胸部上中部を占拠する癌が発見され, 生検組織診および捺印細胞診により未分化小細胞癌と診断された. 術前照射で癌巣の縮小を図り, 根治手術を施行したが, 脳を含む全身諸臓器につぎつぎと転移巣が現れ, 術後10ヵ月で死亡した. 癌細胞は, 概して小型で結合性に乏しく孤立散在性の分布を示していた. ごく一部で小塊形成を伴い, 免疫抗体法でcytokeratin陽性, 電顕的にdesmosomal attachmentが証明された. しかし扁平上皮や腺上皮への分化は確認されなかった. またargyrophiliaやneurosecretory granulesは存在せず, 神経内分泌細胞への分化も認められなかった. 本癌は食道上皮のtotipotent primitivecellに由来した未分化細胞癌と理解された. 食道・未分化小細胞癌は, 従来報告が少ないが, 必ずしも発生頻度の低いものでなく, その存在が広く認識されるにつれ増加するものと予想される.

SUMMARYIgA nephropathy (IgAN) is generally thought to be mediated by the glomerular deposition of circulating immune complexes containing IgA as the major antibody component. Upper respiratory infections and tonsillitis often precede IgAN. and in some cases tonsillectomy is affective for the (treatment of IgAN. Thus, the tonsil seems to be a unique organ causing initial and/or progressive events to generate nephritogenic immune complexes in IgAN. in this study we focused on the analysis of immunopathological features of the palatine tonsil characteristic of IgAN patients by using an immunohistochemical technique. The IgAl subclass was demonstrated in follicular dendritic cells (FDC) of the tonsil of IgAN patients, but not in FDC of non-IgAN controls. On the other hand, IgA2, IgG, IgM and C3 did not show any differences in distribution between the two groups. Moreover, the expression of decay-accelerating factor (DAF), an inhibitor of homologous complement activation, and transforming growth factor-beta I (TGF-/β1). an inducer of antibody-producing ceils to IgA class switching, in FDC and interdigitating dendritic cells of the tonsil, respectively, which was also clarified in this study for the first time, was found to be identically distributed in the two groups. These findings may support the idea that IgA1. possibly in an immune complex form, is trapped by FDC and plays an important role in the persistent activation of particular B cell repertoires responsible for ihe onset and/or progression of IgAN.