RESUMO
The question of whether spatial attention can modulate initial afferent activity in area V1, as measured by the earliest visual event-related potential (ERP) component "C1", is still the subject of debate. Because attention always enhances behavioral performance, previous research has focused on finding evidence of attention-related enhancements in visual neural responses. However, recent psychophysical studies revealed a complex picture of attention's influence on visual perception: attention amplifies the perceived contrast of low-contrast stimuli while dampening the perceived contrast of high-contrast stimuli. This evidence suggests that attention may not invariably augment visual neural responses but could instead exert inhibitory effects under certain circumstances. Whether this bi-directional modulation of attention also manifests in C1 and whether the modulation of C1 underpins the attentional influence on contrast perception remain unknown. To address these questions, we conducted two experiments (N = 67 in total) by employing a combination of behavioral and ERP methodologies. Our results did not unveil a uniform attentional enhancement or attenuation effect of C1 across all subjects. However, an intriguing correlation between the attentional effects of C1 and contrast appearance for high-contrast stimuli did emerge, revealing an association between attentional modulation of C1 and the attentional modulation of contrast appearance. This finding offers new insights into the relationship between attention, perceptual experience, and early visual neural processing, suggesting that the attentional effect on subjective visual perception could be mediated by the attentional modulation of the earliest visual cortical response.
Assuntos
Eletroencefalografia , Córtex Visual , Humanos , Potenciais Evocados Visuais , Córtex Visual/fisiologia , Mapeamento Encefálico/métodos , Estimulação Luminosa/métodos , Percepção Visual/fisiologia , Potenciais Evocados , Atenção/fisiologiaRESUMO
Major depressive disorder (MDD) is a complex state-dependent psychiatric illness for which biomarkers linking psychophysical, biochemical, and psychopathological changes remain yet elusive, though. Earlier studies demonstrate reduced GABA in lower-order occipital cortex in acute MDD leaving open its validity and significance for higher-order visual perception, though. The goal of our study is to fill that gap by combining psychophysical investigation of visual perception with measurement of GABA concentration in middle temporal visual area (hMT+) in acute depressed MDD. Psychophysically, we observe a highly specific deficit in visual surround motion suppression in a large sample of acute MDD subjects which, importantly, correlates with symptom severity. Both visual deficit and its relation to symptom severity are replicated in the smaller MDD sample that received MRS. Using high-field 7T proton Magnetic resonance spectroscopy (1H-MRS), acute MDD subjects exhibit decreased GABA concentration in visual MT+ which, unlike in healthy subjects, no longer correlates with their visual motion performance, i.e., impaired SI. In sum, our combined psychophysical-biochemical study demonstrates an important role of reduced occipital GABA for altered visual perception and psychopathological symptoms in acute MDD. Bridging the gap from the biochemical level of occipital GABA over visual-perceptual changes to psychopathological symptoms, our findings point to the importance of the occipital cortex in acute depressed MDD including its role as candidate biomarker.
Assuntos
Transtorno Depressivo Maior , Depressão , Humanos , Lobo Occipital/química , Espectroscopia de Prótons por Ressonância Magnética , Percepção Visual , Ácido gama-AminobutíricoRESUMO
Healthy individuals are usually biased toward small numbers when they are asked to mentally bisect number intervals or generate number sequences. Number magnitude may be represented spatially along a left-to-right mental number line. The preference for small numbers is believed to reflect the leftward spatial bias of this numerical representation. This study examined whether small numbers captured visual attention more than larger numbers. Participants were asked to detect a target pre-cued by a small or a large number. We found that the response was faster when the target was pre-cued by a small number than when pre-cued by a large number, suggesting that visual attention is preferentially allocated to small numbers. In addition, this attentional preference for small numbers was distinct for participants of different educational backgrounds. For science or engineering participants, this small number preference was enhanced by left-hand responding and was positively correlated with the small number preference in a random number generation task, suggesting that the small number preference was attributable to a leftward bias of the spatial representation. For liberal arts participants, however, left-hand responding did not enhance the small number preference and no correlations were found between the attention task and the random number generation task, suggesting that non-spatial processing mediated the small number preference. Our findings show that the small number preference occurs as early as the perceptual processing stage and distinct mechanisms underlie the preference for small numbers for participants with different educational backgrounds.
Assuntos
Atenção/fisiologia , Sinais (Psicologia) , Conceitos Matemáticos , Reconhecimento Visual de Modelos/fisiologia , Percepção Espacial/fisiologia , Adolescente , Análise de Variância , Feminino , Lateralidade Funcional , Mãos , Humanos , Masculino , Estimulação Luminosa , Psicofísica , Tempo de Reação/fisiologia , Estatística como Assunto , Fatores de Tempo , Adulto JovemRESUMO
In this study, we investigated whether the numerical information of a digit would affect perceptual processing speed for that digit. In Experiment 1, participants performed a temporal order judgment (TOJ) task in which they judged the order of two digits presented briefly to the left or right of the fixation point with a short asynchrony. The point of subjective simultaneity (PSS) was significantly shifted such that large numbers had to be presented before small numbers in order to be perceived as simultaneous, implying that small numbers are perceptually processed faster than large numbers. Given the susceptibility of a TOJ task to response bias, this result might have simply reflected the conceptual association between magnitude (e.g., small) and response selection (e.g., first). To exclude the potential influence of response bias, we adopted a simultaneity judgment (SJ) task in Experiment 2. Most participants in Experiment 2 had participated in Experiment 1. The participants judged whether the two digits were presented simultaneously or successively. The maximal possibility of simultaneous response was obtained when a large digit preceded a small digit by 5 ms, suggesting that small numbers were indeed perceived earlier than large numbers. Our findings indicated that small numbers were processed faster than large ones and that perceptual mechanisms contribute to this temporal advantage. In addition, although the TOJ and SJ task produced a similar processing speed advantage for small numbers, the PSSs of the two tasks were not correlated, which implied that different cognitive mechanisms were involved in the two tasks.
Assuntos
Julgamento/fisiologia , Percepção de Movimento/fisiologia , Percepção do Tempo/fisiologia , Feminino , Humanos , Masculino , Estimulação Luminosa , Tempo de Reação/fisiologia , Adulto JovemRESUMO
In a conventional (Stroop) priming paradigm, it was well documented that objective prime-target incongruency delays response time (RT) to target compared to prime-target congruent condition. Recent evidence suggests that incongruency between the target and subjectively reported prime identity also delays RT over and above the classic congruency effect. When the prime is rendered invisible, the former effect is fundamentally a bottom-up (BU) stimulus-driven congruency effect and the latter a top-down (TD) guess-driven congruency effect. An influential theory of consciousness, global neuronal workspace theory, postulates that the long-lasting simultaneous and reciprocal interaction between TD decision network and BU input network is preserved during conscious processing and disabled during unconscious processing. Current study is focused on testing this theoretical postulation using two behavioral experiments. Our results showed that indeed TD-congruency and BU-congruency produced additive RT effects on prime-invisible trials, which implies that TD and BU prime representations are activated in independent neuronal populations. Meanwhile, an underadditive interaction effect was observed as prime visibility rose, which is a signature that TD and BU prime representations recruited overlapping neuronal populations during conscious perception. In addition, we suggest that current behavioral paradigm might be a financially friendly alternative to detect the presence of representational overlap in the brain between a wide range of mental representations, such as expectation, prediction, conscious/unconscious perception, and conscious/unconscious working memory. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Assuntos
Encéfalo , Estado de Consciência , Humanos , Estado de Consciência/fisiologia , Tempo de Reação , Conscientização/fisiologiaRESUMO
There has been enduring debate on how attention alters contrast appearance. Recent research indicates that exogenous attention enhances contrast appearance for low-contrast stimuli but attenuates it for high-contrast stimuli. Similarly, one study has demonstrated that endogenous attention heightens perceived contrast for low-contrast stimuli, yet none have explored its impact on high-contrast stimuli. In this study, we investigated how endogenous attention alters contrast appearance, with a specific focus on high-contrast stimuli. In Experiment 1, we utilized the rapid serial visual presentation (RSVP) paradigm to direct endogenous attention, revealing that contrast appearance was enhanced for both low- and high-contrast stimuli. To eliminate potential influences from the confined attention field in the RSVP paradigm, Experiment 2 adopted the letter identification paradigm, deploying attention across a broader visual field. Results consistently indicated that endogenous attention increased perceived contrast for high-contrast stimuli. Experiment 3 employed equiluminant chromatic letters as stimuli in the letter identification task to eliminate potential interference from contrast adaption, which might have occurred in Experiment 2. Remarkably, the boosting effect of endogenous attention persisted. Combining the results from these experiments, we propose that endogenous attention consistently enhances contrast appearance, irrespective of stimulus contrast levels. This stands in contrast to the effects of exogenous attention, suggesting that mechanisms through which endogenous attention alters contrast appearance may differ from those of exogenous attention.
RESUMO
Spatial attention is generally believed to increase contrast appearance of visual stimuli. A recent study, however, revealed that attention attenuates appearance of high-contrast stimuli. This puzzling attentional attenuation was ascribed to the attentional modulation on supersaturating neurons, whose response initially increases to peak and then decreases as stimulus intensity increases. Here, in two experiments (N = 22), we examined this hypothesis by testing how contrast adaptation affects attentional modulation on contrast appearance of high-contrast stimuli. We found that luminance-contrast adaptation reversed attentional effects from attenuation to enhancement, supporting the supersaturation model. Moreover, equiluminant red-green adaptation only vanished but could not reverse the attentional attenuation, implying that the parvocellular pathway was not the dominant pathway mediating the attentional attenuation. Our study indicates that supersaturation, as a pervasive phenomenon in neuronal responses, can be manifested in attentional modulation on perceived contrast, and the M-pathway may play an important role in this attentional processing. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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Atenção , Atenção/fisiologia , Humanos , Estimulação LuminosaRESUMO
Center-surround antagonism, as a ubiquitous feature in visual processing, usually leads to inferior perception for a large stimulus compared to a small one. For example, it is more difficult to judge the motion direction of a large high-contrast pattern than that of a small one. However, this spatial suppression in the motion dimension was only reported for luminance motion, and was not found for chromatic motion. Given that center-surround suppression only occurs for strong visual inputs, we hypothesized that previous failure in finding spatial suppression of chromatic motion might be due to weak chromatic motion being induced with stimuli of limited parameters. In this study, we used phase-shift discrimination and motion-direction discrimination tasks to measure motion spatial suppression induced by stimuli of two spatial frequencies (0.5 and 2 cpd) and two contrasts (low and high). We found that spatial suppression of the chromatic motion was stably observed for stimuli of high spatial frequency (2 cpd) and high contrast and spatial summation occurred for stimuli of low spatial frequency (0.5 cpd). Intriguingly, there was no correlations between the motion spatial suppressions of luminance motion and chromatic motion, implying that the two types of spatial suppression are not originated from the same neural processing. Our findings indicate that spatial suppression also exists for chromatic motion, and the mechanisms underlying the spatial suppression of chromatic motion is different from that of luminance motion.
Assuntos
Percepção de Cores , Percepção de Movimento , Sensibilidades de Contraste , Humanos , Movimento (Física) , Psicofísica , Percepção VisualRESUMO
How perceived size (length) of an object is influenced by attention is in debate. Prism adaptation (PA), as a type of sensory motor adaptation, has been shown to affect performance on a variety of spatial tasks in both neglect patient and healthy individuals. It has been hypothesized that PA's effects might be mediated by attentional mechanisms. In this study, we used PA to laterally shift spatial attention, and employed a precise psychophysical procedure to examine how the perceptual length of lines was influenced by this attentional shifting. Participants were presented with two separate lines in the left and right visual fields, and compared the length of the two lines. Forty-five healthy participants completed this line-length judgment task before and after a short period of adaptation to either left- (Experiment 1) or right-shifting (Experiment 2) prisms, or control goggles that did not shift the visual scene (Experiment 3). We found that participants initially tended to perceive the line presented in the left to be longer. This leftward bias of length perception was reduced by a short period of visuomotor adaptation to the left-deviating PA. However, for the right-shifting PA and plain glass goggles conditions, the initial length perception bias to the left line was unaffected. Mechanisms of this asymmetric effect of PA was discussed. Our results demonstrate that the length perception of a line can be influenced by a simple visuomotor adaptation, which might shift the spatial attention. This finding is consistent with the argument that attention can alter appearance.
RESUMO
Does attention alter appearance? Recent studies have shown that an exogenous cue tends to increase the perceived contrast of a low-contrast stimulus. In the present study we systematically studied the attentional effect over a wide range of contrast levels (15% to 60%). Besides replicating the enhancement at lower contrast levels with higher comparative tasks (Experiment 1), the data revealed a cue-induced attenuation in apparent contrast at higher contrast levels with lower comparative tasks (Experiment 2) and same/different judgment task (Experiment 3). This attenuation effect was robust at the individual level, and it was not due to response bias or sensory interactions (Experiments 3 and 4). These results suggest that attention modulates contrast appearance and this effect depends on both the contrast level and the type of judgment task used. We propose that our findings can be understood through contrast gain mechanism on supersatuating neurons, whose response increases first as the stimulus intensity increases, but decrease the responses after the peak. This surprising phenomenon offers insights for the underlying neural mechanisms of visual processing. (PsycINFO Database Record
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Atenção/fisiologia , Sensibilidades de Contraste/fisiologia , Sinais (Psicologia) , Desempenho Psicomotor/fisiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Several types of suppression phenomena have been observed in the visual system. For example, the ability to detect a target stimulus is often impaired when the target is embedded in a high-contrast surround. This contextual modulation, known as surround suppression, was formerly thought to occur only in the periphery. Another type of suppression phenomena is interocular suppression, in which the sensitivity to a monocular target is reduced by a superimposed mask in the opposite eye. Here, we explored how the two types of suppression operating across different spatial regions interact with one another when they simultaneously exert suppressive influences on a common target presented at the fovea. In our experiments, a circular target grating presented to the fovea of one eye was suppressed interocularly by a noise pattern of the same size in the other eye. The foveal stimuli were either shown alone or surrounded by a monocular annular grating. The orientation and eye-of-origin of the surround grating were varied. We found that the detection of the foveal target subjected to interocular suppression was severely impaired by the addition of the surround grating, indicating strong surround suppression in the fovea. In contrast, when the interocular suppression was released by superimposing a binocular fusion ring onto both the target and the dichoptic mask, the surround suppression effect was found to be dramatically decreased. In addition, the surround suppression was found to depend on the contrast of the dichoptic noise with the greatest surround suppression effect being obtained only when the noise contrast was at an intermediate level. These findings indicate that surround suppression and interocular suppression are not independent of each other, but there are strong interactions between them. Moreover, our results suggest that strong surround suppression may also occur at the fovea and not just the periphery.
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Visão Binocular/fisiologia , Visão Ocular/fisiologia , Sensibilidades de Contraste , Humanos , Estimulação Luminosa , Limiar SensorialRESUMO
The presence of autoantibodies in New Zealand Black (NZB) mice suggests a B cell tolerance defect however the nature of this defect is unknown. To determine whether defects in B cell anergy contribute to the autoimmune phenotype in NZB mice, soluble hen egg lysozyme (sHEL) and anti-HEL Ig transgenes were bred onto the NZB background to generate double transgenic (dTg) mice. NZB dTg mice had elevated levels of anti-HEL antibodies, despite apparently normal B cell functional anergy in-vitro. NZB dTg B cells also demonstrated increased survival and abnormal entry into the follicular compartment following transfer into sHEL mice. Since this process is dependent on BAFF, BAFF serum and mRNA levels were assessed and were found to be significantly elevated in NZB dTg mice. Treatment of NZB sHEL recipient mice with TACI-Ig reduced NZB dTg B cell survival following adoptive transfer, confirming the role of BAFF in this process. Although NZB mice had modestly elevated BAFF, the enhanced NZB B cell survival response appeared to result from an altered response to BAFF. In contrast, T cell blockade had a minimal effect on B cell survival, but inhibited anti-HEL antibody production. The findings suggest that the modest BAFF elevations in NZB mice are sufficient to perturb B cell tolerance, particularly when acting in concert with B cell functional abnormalities and T cell help.
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Fator Ativador de Células B/sangue , Fator Ativador de Células B/imunologia , Linfócitos B/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Linfócitos T/imunologia , Animais , Autoanticorpos/imunologia , Linfócitos B/metabolismo , Tolerância Imunológica/genética , Tolerância Imunológica/imunologia , Lúpus Eritematoso Sistêmico/genética , Camundongos , Camundongos Transgênicos , Muramidase/genética , Muramidase/fisiologia , Linfócitos T/metabolismoRESUMO
INTRODUCTION: Systemic lupus erythematosus is a genetically complex disease. Currently, the precise allelic polymorphisms associated with this condition remain largely unidentified. In part this reflects the fact that multiple genes, each having a relatively minor effect, act in concert to produce disease. Given this complexity, analysis of subclinical phenotypes may aid in the identification of susceptibility alleles. Here, we used flow cytometry to investigate whether some of the immune abnormalities that are seen in the peripheral blood lymphocyte population of lupus patients are seen in their first-degree relatives. METHODS: Peripheral blood mononuclear cells were isolated from the subjects, stained with fluorochrome-conjugated monoclonal antibodies to identify various cellular subsets, and analyzed by flow cytometry. RESULTS: We found reduced proportions of natural killer (NK)T cells among 367 first-degree relatives of lupus patients as compared with 102 control individuals. There were also slightly increased proportions of memory B and T cells, suggesting increased chronic low-grade activation of the immune system in first-degree relatives. However, only the deficiency of NKT cells was associated with a positive anti-nuclear antibody test and clinical autoimmune disease in family members. There was a significant association between mean parental, sibling, and proband values for the proportion of NKT cells, suggesting that this is a heritable trait. CONCLUSIONS: The findings suggest that analysis of cellular phenotypes may enhance the ability to detect subclinical lupus and that genetically determined altered immunoregulation by NKT cells predisposes first-degree relatives of lupus patients to the development of autoimmunity.
Assuntos
Autoimunidade/imunologia , Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Células T Matadoras Naturais/imunologia , Adulto , Anticorpos Antinucleares/sangue , Antígenos CD/metabolismo , Família , Feminino , Citometria de Fluxo , Humanos , Lúpus Eritematoso Sistêmico/sangue , Masculino , Linhagem , FenótipoRESUMO
Previous mapping studies have linked New Zealand Black (NZB) chromosome 4 to several lupus traits, including autoantibody production, splenomegaly, and glomerulonephritis. To confirm the presence of these traits, our laboratory introgressed homozygous NZB chromosome 4 intervals extending from either 114 to 149 Mb or 32 to 149 Mb onto the lupus-resistant C57BL/6 background (denoted B6.NZBc4S and B6.NZBc4L, respectively). Characterization of aged cohorts revealed that B6.NZBc4L mice exhibited a striking increase in splenic B1a and NKT cells in the absence of high titer autoantibody production and significant renal disease. Tissue-specific expansion of these subsets was also seen in the peritoneum and liver for B1a cells and in the bone marrow for NKT cells. Staining with CD1d tetramers loaded with an alpha-galactosylceramide analog (PBS57) demonstrated that the expanded NKT cell population was mainly CD1d-dependent NKT cells. The lack of both cellular phenotypes in B6.NZBc4S mice demonstrates that the genetic polymorphism(s) that result in these phenotypes are on the proximal region of NZB chromosome 4. This study confirms the presence of a locus that promotes the expansion of B1a cells and newly identifies a region that promotes CD1d-restricted NKT cell expansion on NZB chromosome 4. Taken together, the data indicate that neither an expansion of B1a cells and/nor NKT cells is sufficient to promote autoantibody production and ultimately, renal disease.
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Autoanticorpos/biossíntese , Proliferação de Células , Nefropatias/imunologia , Células Matadoras Naturais/citologia , Células Matadoras Naturais/imunologia , Animais , Formação de Anticorpos , Antígenos CD1 , Antígenos CD1d , Mapeamento Cromossômico , Cromossomos de Mamíferos , Feminino , Lúpus Vulgar/genética , Camundongos , Camundongos Congênicos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NZB , Baço/citologiaRESUMO
Polyclonal B cell activation is a prominent feature of the lupus-prone New Zealand Black (NZB) mouse strain. We have previously demonstrated linkage between a region on NZB chromosome 13 and increased costimulatory molecule expression on B cells. In this study we have produced C57BL/6 congenic mice with an introgressed homozygous NZB interval extending from approximately 24 to 73 cM on chromosome 13 (denoted B6.NZBc13). We show that B6.NZBc13 female mice not only have enhanced B cell activation but also share many other B cell phenotypic characteristics with NZB mice, including expansion of marginal zone and CD5+ B cell populations, increased numbers of IgM ELISPOTs, and increased serum levels of total IgM and IgM autoantibodies. In addition these mice have increased T cell activation, increased numbers of germinal centers, mild glomerulonephritis, and produce high-titer IgM and IgG anti-chromatin Abs. Male B6.NZBc13 mice have a less pronounced cellular phenotype, lacking expansion of the marginal zone B cell population and IgG anti-chromatin Ab production, indicating the presence of gender dimorphism for this locus. Thus, we have identified a genetic locus that recapitulates with fidelity the B cell phenotypic abnormalities in NZB mice, and we demonstrate that this locus is sufficient to induce an autoimmune phenotype. The data provide further support to the contention that immune abnormalities leading to altered B cell activation and selection contribute to the development of autoimmunity in NZB mice.
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Autoanticorpos/biossíntese , Linfócitos B/imunologia , Mapeamento Cromossômico , Ativação Linfocitária/imunologia , Baço/imunologia , Animais , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Linfócitos B/metabolismo , Feminino , Citometria de Fluxo , Imunofluorescência , Camundongos , Camundongos Congênicos , Camundongos Endogâmicos NZB , Baço/citologia , Linfócitos T/imunologiaRESUMO
Genetic loci on New Zealand Black (NZB) chromosome 1 play an important role in the development of lupus-like autoimmune disease. We have shown previously that C57BL/6 mice with an introgressed NZB chromosome 1 interval extending from approximately 35 to 106 cM have significantly more severe autoimmunity than mice with a shorter interval extending from approximately 82 to 106 cM. Comparison of the cellular phenotype in these mice revealed that both mouse strains had evidence of increased T cell activation; however, activation was more pronounced in mice with the longer interval. Mice with the longer interval also had increased B cell activation, leading us to hypothesize that there were at least two independent lupus susceptibility loci on chromosome 1. In this study, we have used mixed hemopoietic radiation chimeras to demonstrate that autoimmunity in these mice arises from intrinsic B and T cell functional defects. We further show that a T cell defect, localized to the shorter interval, leads to spontaneous activation of T cells specific for nucleosome histone components. Despite activation of self-reactive T cells in mixed chimeric mice, only chromosome 1 congenic B cells produce anti-nuclear Abs and undergo class switching, indicating impaired B cell tolerance mechanisms. In mice with the longer chromosome 1 interval, an additional susceptibility locus exacerbates autoimmune disease by producing a positive feedback loop between T and B cell activation. Thus, T and B cell defects act in concert to produce and amplify the autoimmune phenotype.
Assuntos
Doenças Autoimunes/imunologia , Linfócitos B/patologia , Linfócitos T/patologia , Animais , Anticorpos Antinucleares/biossíntese , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/patologia , Doenças Autoimunes/patologia , Autoimunidade/genética , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Comunicação Celular/imunologia , Proliferação de Células , Células Cultivadas , Cromossomos de Mamíferos , Switching de Imunoglobulina , Ativação Linfocitária , Camundongos , Camundongos Congênicos , Camundongos Endogâmicos NZB , Linfócitos T/imunologiaRESUMO
In previous work, we demonstrated linkage between a broad region on New Zealand Black (NZB) chromosome 1 and increased costimulatory molecule expression on B cells and autoantibody production. In this study, we produced C57BL/6 congenic mice with homozygous NZB chromosome 1 intervals of differing lengths. We show that both B6.NZBc1(35-106) (numbers denote chromosomal interval length) and B6.NZBc1(85-106) mice produce IgG anti-nuclear autoantibodies, but B6.NZBc1(35-106) mice develop significantly higher titers of autoantibodies and more severe renal disease than B6.NZBc1(85-106) mice. Cellular analysis of B6.NZBc1(85-106) mice revealed splenomegaly and increased numbers of memory T cells. In addition to these features, B6.NZBc1(35-106) mice had altered B and T cell activation with increased expression of CD69, and for B cells, costimulatory molecules and MHC. Introduction of an anti-hen egg white lysozyme Ig transgene, as a representative nonself-reactive Ig receptor, onto the B6.NZBc1(35-106) background corrected the B cell activation phenotype and led to dramatic normalization of splenomegaly and T cell activation, but had little impact on the increased proportion of memory T cells. These findings indicate that there are multiple lupus susceptibility genes on NZB chromosome 1, and that although B cell defects play an important role in lupus pathogenesis in these mice, they act in concert with T cell activation defects.