Individual Repertoires Research Articles

VH genes expressed in peripheral blood IgE-producing B cells from patients with atopic dermatitis.

In this study we analysed the VH genes expressed in IgE-producing peripheral B cells in two patients with severe atopic dermatitis. We found a diverse antibody repertoire containing V(H) genes of five different VH families, no VH2 and 7 genes, with no biased usage of one particular VH gene family. Some VH germ-line segments were found to be used several times within the epsilon transcripts (V3-23, V3-30). Comparison of the IgE-encoding VH genes with the respective germ-line elements revealed the expression of nearly germ-line identical as well as somatically mutated VH genes. In these latter VH genes base substitutions were distributed over both complementarity determining and framework regions. Because of the similarities between the IgE committed B cell repertoire in atopic patients and the peripheral B cell repertoire in non-atopic individuals we conclude that the atopic VH gene repertoire probably reflects the result of an increased class switch of polyclonal B cells, including virgin and mature B cells, in response to a Th2 cytokine profile.

Antibody penetration into living cells: pathogenic, preventive and immuno-therapeutic implications.

The dogmatic and at one time prevalent concept that intact antibody molecules were not able to enter into viable cells has now been modified due to the availability of a large amount of experimental findings and clinical observations that indicate otherwise. Penetration of mature autoantibodies into living cells might participate in the pathogenesis of diverse autoimmune diseases, through inducing apoptosis of healthy tissues and cells, but also by contributing to the breakdown of self-tolerance through presentation of self-antigens to the immune system. Conversely, the penetration of naturally occurring autoantibodies into immature lymphoid cells might have a physiological role in the edition of the immune repertoire in healthy individuals. Increasing interest is being paid to the potential immunotherapeutic role of penetrating antibodies as tools to deliver drugs, isotopes or genes into cells.

Five potential principles for understanding cultural differences in relation to individual differences

This paper deals with psychological differences between two cultures, with respect to the differences between individuals in those same cultures. Five principles are presented which describe either actual or probable empirical relationships between within- and between-culture differences, and a possible theoretical account is given for each of the presumed differences. (1) The differences between “cultures” seem “bigger” than the actual differences between the individuals in these same cultures. This relation is attributed to the idea that universal human biological predispositions are often opposed by cultural traditions, so the outcome is somewhat of a compromise between the two. (2) Differences between individuals in different cultures are generally larger in behavior than in thoughts or feelings This is attributed to the fact that it is easier to socialize behavior than mental events. (3) Many cultural differences are expressed in individuals in terms of different default responses or interpretations or preferences for the same situation. Dominant responses in one culture are usually a less salient part of the repertoire of individuals in another culture. (4) Much of the effect of culture, and our impression of culture differences, results from the physical/social artifacts (environments, institutions) created by the culture. There is a strong tendency by psychologists to under-rate or ignore the effects of the physical environment. (5) In the contemporary world, differences between individuals in two cultures will be larger in older generations. Cultural differences may be markedly reduced in the most recent generations, on account of globalization. The position put forth is an attempt to integrate the ideas that there are real human predispositions of various sorts and that culture is a powerful force, and to explain why it is surprisingly easy for us to understand the viewpoint of people from other cultures (their “reality”is often a less preferred alternative in our own repertoire).

Some theoretical implications

AGREAT DEAL of the most exciting current work in American speech involves what has recently come to be called "variation theory."' Stemming particularly from the work of William Labov,2 variation theory is premised in large part upon a reevaluation of the structuralist concept of "free variation" (as in, for example, the "free variation" between the pronunciation /-in/ and the pronunciation /-io/ for the morpheme {-ing}). Linguists have long recognized that speech communities, and even individual speakers, are not always consistent in the application of many linguistic rules and that this variety is at least sometimes associated with social class, formality levels, and so on.3 What variationists have discovered is the extraordinary stylistic and sociological importance of such variation, and the apparently remarkable consistency with which the frequency of a given alternant is patterned throughout society and throughout an individual's stylistic repertoire. One well-known example involves the variable presence or absence of {-Z} morphemes in the speech of American blacks. One findsin, say, the transcript of the informal conversation of an adolescent street gang in an urban ghetto-two book beside two books ({-Z1}), the boy hat beside the boy's hat ({-Z2}), and the man go beside the man goes ({-Z3}). With such a group under such circumstances, {-Z} tends to be quite rare; as the formality level increases, however, so does the presence of {-Z}. Likewise, almost any other social group would show a higher percentage of {-Z}, for it is more common among females than males, and increases with age and higher social class.

Is there a French theory of variation?

Does French work on variation simply follow the theory proposed by the American sociolinguist William Labov, or does it possess its own approach, which, while making use of the same term, variation, has developed independently? Since the theoretical and political environment in France has never really been adapted to the study of diversity and variation in language, it is only recently that certain linguists (not necessarily sociolinguists) have developed endogenous themes as far as variation is concerned. Their contributions touch on two crucial areas for any theory of variation: on the one hand, the opposition between phonology and syntax (an area in which different forms yield different meanings) and, on the other hand, individual speech repertoires and stylistic diversity.

The Social Context of Applied Science: A Model Undergraduate Program

This article justifies the inclusion of social context in innovative undergraduate applied science programs. It proposes a model social context program, distinguishing it from two inferior strategies that expose students to a range of social disciplines at too elementary a level or rely on unsystematic, anecdotal work experience of science faculty confronting regulatory events. The article describes stresses associated with implementing the model program. Finally, it discusses the relationship of the model program to trends in higher education. A social context curriculum should explore the tensions between knowledge and power and give students practice in institutional design. It should encourage both engagement and skepticism. Graded case studies, simulations, senior projects, and experiential elements should be used to introduce a typology of institutional designs and progressively develop students’ individual design repertoires. Implementation stresses come from debates over content, interdisciplinarity, university and departmental governance, and the reform of higher education, generally.

An Investigation of Members’ Roles in Wind Quintets

This article presents new findings regarding group processes in chamber ensembles. Following work by Young and Colman, Butterworth, and Murnighan and Conlon on the string quartet, a questionnaire was distributed to wind quintets throughout the UK. A total of 55 respondents, representing 20 ensembles, participated in the study. Quantitative and qualitative data revealed information about group formation, personnel recruitment and the use of deputies, leadership, seating positions, verbal and non-verbal communication, conflict, rehearsing and performing, audience effects, social aspects and administration. The current study focuses on the role of the horn player in the quintet and explores players’ attitudes and perceptions of their individual careers, quintet repertoire, concert promoters and string quartets as an opposing medium. Results are discussed with reference to the existing quartet studies and to social psychological theory of group dynamics.

Temporal variation in male chaffinch song depends on the singer and the song type

Studies of variation in bird song within a species have tended to concentrate on repertoire size and on song rate, while other aspects of song delivery have received little attention even though they are also likely to play an important part in the signalling process. We here examine the pattern of delivery of individual males' repertoires in the chaffinch (Fringilla coelebs) to identify variation in a range of temporal parameters of song delivery. Coefficients of variation differed between song units and across hierarchical levels. Basic units (syllables) were delivered with great temporal precision. The larger building blocks of a song (the different phrases and the flourish) showed the highest variability while variation for song duration itself was intermediate. Most variables showed consistent differences between males, but there were also consistent differences between song types within a male's repertoire, as well as between the same song types as sung by different males. This suggests an interaction between a male's phenotype and song production, but because of consistent differences between song types within repertoires, there is potential for selection to act on aspects of song delivery both of the individual and of the song type (i.e. the culturally transmitted unit).

The relational self: an interpersonal social-cognitive theory.

The authors propose an interpersonal social-cognitive theory of the self and personality, the relational self, in which knowledge about the self is linked with knowledge about significant others, and each linkage embodies a self-other relationship. Mental representations of significant others are activated and used in interpersonal encounters in the social-cognitive phenomenon of transference (S. M. Andersen & N. S. Glassman, 1996), and this evokes the relational self. Variability in relational selves depends on interpersonal contextual cues, whereas stability derives from the chronic accessibility of significant-other representations. Relational selves function in if-then terms (W. Mischel & Y. Shoda, 1995), in which ifs are situations triggering transference, and thens are relational selves. An individual's repertoire of relational selves is a source of interpersonal patterns involving affect, motivation, self-evaluation, and self-regulation.

Endogenous H/K ATPase beta-subunit promotes T cell tolerance to the immunodominant gastritogenic determinant.

A CD4(+) T cell response to the gastric H/K ATPase beta-subunit (H/Kbeta) is required for the onset of experimental autoimmune gastritis in BALB/c mice. The extent to which endogenous H/Kbeta contributes toward the tolerance of the H/Kbeta-specific T cell repertoire in normal individuals is not known. By comparison of T cell responses in H/Kbeta-deficient (o/o) and H/Kbeta-expressing BALB/c mice, in this work we show that the endogenous H/Kbeta autoantigen plays a major role in the tolerance of pathogenic H/Kbeta-specific T cells. First, T cell-dependent Ab responses to the H/Kbeta Ag were enhanced in H/K ATPase-immunized H/Kbeta-deficient mice compared with wild-type mice. Second, peptide immunization experiments indicated that immune responses to the major gastritogenic epitope of the H/K ATPase, namely H/Kbeta(253-277), were significantly more vigorous in H/Kbeta-deficient mice compared with wild-type mice. Third, unfractionated splenocytes from H/Kbeta-deficient mice, but not H/Kbeta-expressing mice, induced autoimmune gastritis after adoptive transfer to BALB/c nude mice. The enhanced responses to H/Kbeta in H/Kbeta-deficient mice were shown to be intrinsic to CD4(+)CD25(-) T cells rather than a change in status of CD4(+)CD25(+) regulatory T cells. We conclude from these studies that the H/Kbeta-specific T cells in wild-type mice represent the residue of a T cell repertoire, directed toward a single determinant, that has been subjected to partial tolerance induction.

Estudos sobre autismo em análise do comportamento: aspectos metodológicos

A pesquisa na Análise do Comportamento tem contribuído para a identificação e compreensão das variáveis que afetam o repertório de indivíduos autistas. Este trabalho visou identificar aspectos metodológicos na produção desta área com essa população. A análise dos trabalhos identificou duas linhas distintas, porém complementares, de pesquisa. Uma delas parece buscar a identificação das variáveis que atuam no estabelecimento de controle de estímulos. A outra procura o estabelecimento e manutenção de operantes verbais. Os aspectos metodológicos analisados foram a natureza dos estímulos utilizados, os critérios de escolha dos mesmos, tipos de resposta requerida e tipos de conseqüências disponibilizadas. São discutidos os benefícios de atentar para as demandas metodológicas da pesquisa analítico-comportamental. Discute-se, ainda, o papel dos analistas do comportamento diante da relativa carência de trabalhos sobre o assunto e da necessidade de desenvolvimento de programas de prevenção e de educação de pais e familiares de pessoas portadoras de autismo.

Genetic Control of Human NK Cell Repertoire

Through differential killer cell Ig-like receptor (KIR) and CD94:NKG2 gene expression, human NK cells generate diverse repertoires, each cell having an inhibitory receptor for autologous HLA class I. Using a new method for measuring repertoire difference that integrates multiple flow cytometry parameters, we found individual repertoire stability, but population variability. Correlating repertoire differences with KIR and HLA genotype for 85 sibling pairs reveals the dominant influence of KIR genotype; HLA genotype having a subtle, modulating effect on relative KIR expression frequencies. HLA and/or KIR genotype also influences CD94:NKG2A expression. After HLA-matched stem cell transplantation, KIR repertoires either recapitulated that of the donor or were generally depressed for KIR expression. Human NK cell repertoires are defined by combinations of variable KIR and HLA class I genes and conserved CD94:NKG2 genes.

T cell response in experimental autoimmune encephalomyelitis (EAE): role of self and cross-reactive antigens in shaping, tuning, and regulating the autopathogenic T cell repertoire.

T cells that can respond to self-antigens are present in the peripheral immune repertoire of all healthy individuals. Recently we have found that unmanipulated SJL mice that are highly susceptible to EAE also maintain a very high frequency of T cells responding to an encephalitogenic epitope of a myelin antigen proteolipid protein (PLP) 139-151 in the peripheral repertoire. This is not due to lack of expression of myelin antigens in the thymus resulting in escape of PLP 139-151 reactive cells from central tolerance, but is due to expression of a splice variant of PLP named DM20, which lacks the residues 116-150. In spite of this high frequency, the PLP 139-151 reactive cells remain undifferentiated in the periphery and do not induce spontaneous EAE. In contrast, SJL TCR transgenic mice expressing a receptor derived from a pathogenic T cell clone do develop spontaneous disease. This may be because in normal mice, autoreactive cells are kept in check by an alternate PLP 139-151 reactive nonpathogenic repertoire, which maintains a balance that keeps them healthy. If this is the case, selective activation of one repertoire or the other may alter susceptibility to autoimmune disease. Since T cells are generally cross-reactive, besides responding to nonself-antigens, they also maintain significant responses to self-antigens. Based on the PLP 139-151 system, we propose a model in which activation with foreign antigens can result in the generation of pathogenic memory T cells that mediate autoimmunity. We also outline circumstances under which activation of self-reactive T cells with foreign antigens can generate selective tolerance and thus generate protective/regulatory memory against self while still maintaining significant responses against foreign antigens. This provides a mechanism by which the fidelity and specificity of the immune system against foreign antigens is improved without increasing the potential for developing an autoimmune disease.

Susceptibility gene discovery for common metabolic and endocrine traits.

Almost all major causes of ill-health and premature death in human societies worldwide - including cancer, cardiovascular disease, diabetes and many infectious diseases - are, at least in part, genetically determined. Typically, risk of succumbing to one of these illnesses is thought to depend on both the individual repertoire of variation within a number of key susceptibility genes and the history of exposure to relevant environmental factors. For many of these conditions, the molecular basis of disease pathogenesis remains obscure. This represents a major obstacle to development of improved, rational strategies for disease treatment, prevention and eradication. It is easy therefore to appreciate the importance attached to efforts to deliver more comprehensive understanding of the molecular basis of disease pathogenesis. Nor is it hard to understand that identification of major susceptibility genes should highlight those components of molecular machinery that are critical for the preservation of normal health. The benefits promised are great, but progress to gene identification in multifactorial traits has been rather disappointing to date. Why is this? This review aims to answer this question by describing current and future approaches to gene discovery in multifactorial traits. The examples quoted will mostly relate to type 2 diabetes, but the issues and approaches are generic, and apply equally to other multifactorial traits in the endocrine and metabolic arena - type 1 diabetes; obesity; hyperlipidaemia; autoimmune thyroid disease; polycystic ovarian syndrome - and beyond.

Autoantibodies against C1q: view on clinical relevance and pathogenic role.

C. E. H. SIEGERT, M. D. KAZATCHKINE*, A. SJO¨HOLM§, R. WU¨RZNER†, M. LOOS‡ & M. R. DAHADepartment of Nephrology, Leiden University Medical Centre, Leiden, The Netherlands, *Institut National de la Sante´et de laRecherche Medicale, Hopital Broussais, Paris, France, † Institut fu¨r Hygiene, Leopold-Franzens-Universita¨t, Innsbruck, Austria,‡ Institute for Medical Microbiology and Hygiene, J-Gutenberg University, Mainz, Germany, and§Clinical Microbiology Laboratory,Lund University Hospital, Lund, Sweden(Accepted for publication 6 January 1999)INTRODUCTIONImmune responses to autoantigens are quite common andautoimmunity is considered to be a physiological part of theimmune system. Autoantibodies are an inherent property of theantibody repertoire of many healthy individuals and are thereforereferred to as natural autoantibodies [1,2]. The numerous kinds ofautoantibodies fall into two main categories, depending on whetherorgan-specific or non-organ-specific autoantigens are involved.Non-organ-specific antigens mostly occur in nucleated cells,such as DNA, or are found among circulating plasma proteins,such as coagulant proteins and the Fc portion of IgG.Natural autoantibodies have been proposed to be involved inthe clearance of degradation products that are formed during cellmetabolism. In this respect natural autoantibodies are also referredto as housekeeping antibodies [3]. Autoantibodies may also beassociated with disease states but do not necessarily play a role inthe pathogenesis of such diseases. The presence of autoantibodiesmay for example be secondary to the production of tissue damage,or independent pathogenic factors may directly induce both thedisease and the presence of autoantibodies.In 1984 autoantibodies to C1q (C1qAb) were reported to bepresent in serum of patients with systemic lupus erythematosus(SLE) [4]. The recognition that C1q may serve as a non-organ-specific autoantigen has attracted a growing number ofinvestigators. This study discusses the knowledge of C1q asautoantigen by reviewing the epidemiology, disease associations,and pathophysiology of C1qAb.ROLE OF C1q IN IMMUNE COMPLEXCLEARANCEActivation of the complement system is the first step in theprevention of damage by immune complexes. Initiation of com-plement activation occurs through three pathways: the classical,the alternative, and the lectin pathway. The classical pathway ofthe complement system is considered to be the most importantpathway in immune complex clearance. This pathway may beactivated by IgM- and IgG-containing immune complexes afterbinding of C1q [5]. C1q is a subcomponent of the first component(C1) of the classical pathway. It is a large highly cationicglycoprotein with a molecular weight of 410kD. C1q consists ofsix copies each of three polypeptide chains, A, B, and C. The A, B,and C chains are rich in hydroxylated amino acids and are linkedtogether by disulphide bonds into dimers [6] Together these dimersform a triple helix structure which resembles collagen. Towardsthe N-terminal end of C1q the triple helices lay parallel to eachother and towards the C-terminal end they diverge. The N-terminalend is called the collagen-like region which is linked by theconnecting strands to the C-terminal end, which is called theglobular heads region. The macromolecular structure of C1q issaid to resemble a bunch of tulips [5–7].The function of C1q is directly related to its structure. Bindingof Fc regions of immunoglobulins to the globular head portions ofC1q induces distortion of the connecting strand which changes theconformation of the collagen-like region [8,9]. The dynamicequilibrium between C1q and the other subcomponents of C1,C1r and C1s, subsequently shifts and induces further activation ofthe cascade of proteins composing the classical pathway. Thisresults in the prevention of lattice formation of immune complexesand ensures their clearance from the circulation by the mono-nuclear phagocyte system [10]. Although the recognition protein ofthe lectin pathway, mannose-binding lectin, is structurally relatedto C1q, it is not known to be involved in immune complexclearance mechanisms [11]. To summarize, activation of C1 bybinding of immune complexes to C1q is a prerequisite for immunecomplex clearance.HISTORY OF C1qAbSince SLE is considered to be the prototype of immune complexdiseases in man, a large variety of immune complex assays hasbeen employed to investigate possible pathogenic roles of circulat-ing immune complexes and to relate their titres to the presence ofmanifestations of the disease. The solid-phase C1q binding assay isone of the most frequently used assays for both purposes [12]. Thisradioimmunoassay is based on the binding of immune complexesto C1q, which is fixed to a solid phase. Studies in the early 1970s

CD4+ and CD8+ clonal T cell expansions indicate a role of antigens in ankylosing spondylitis; a study in HLA-B27+ monozygotic twins.

Ankylosing spondylitis (AS) is a complex genetic disease in which both MHC and non-MHC genes determine disease susceptibility. To determine whether the T cell repertoires of individuals with AS show signs of increased stimulation by exogenous antigens, CD4+ and CD8+ T cell subsets of five monozygotic HLA-B27+ twins (two concordant and three discordant for AS) and CD8+ T cell repertoires of three healthy HLA-B27+ individuals were characterized by TCR beta-chain (TCRB) CDR3 size spectratyping. Selected TCRB-CDR3 spectra were further analysed by BJ-segment analysis and TCRB-CDR3 from expanded T cell clones were sequenced. In an analysis of all data (519/598 possible TCRB-CDR3 spectra), AS was associated with increased T cell oligoclonality in both CD8+ (P = 0.0001) and CD4+ (P = 0.033) T cell subsets. This was also evident when data were compared between individual twins. Nucleotide sequence analysis of expanded CD8+ or CD4+ T cell clones did not show selection for particular TCRB-CDR3 amino acid sequence motifs but displayed sequence homologies with published sequences from intra-epithelial lymphocytes or synovial T cells from rheumatoid arthritis patients. Together, these results provide support for the hypothesis that responses to T cell-stimulating exogenous or endogenous antigens are involved in the induction and/or maintenance of AS.

Enumeration of hepatitis B surface antigen-specific B lymphocytes in responder and non-responder normal individuals vaccinated with recombinant hepatitis B surface antigen.

Determination of the frequency of specific B lymphocytes has important implications for investigation of the immune response to different antigens and pathogens. Unresponsiveness to some viruses and antigens, such as hepatitis B virus (HBV) and its surface antigen (HBsAg), has been attributed to lack or insufficient production of the specific B-cell repertoire. In this study, peripheral blood B lymphocytes of 45 adult normal individuals vaccinated with recombinant hepatitis B vaccine were transformed with Epstein-Barr virus (EBV) and cultured at different dilutions on human fetal fibroblasts as a feeder layer. The vaccinees were classified into good, poor and non-responder groups. Following 2 to 3 weeks of incubation, culture supernatants were collected from wells containing transformed and proliferating B lymphocytes. The supernatants were subsequently screened for the presence of total immunoglobulin and antibody to HBsAg (anti-HBs) by enzyme-linked immunosorbent assay (ELISA). Accordingly, positive and negative wells were enumerated in each plate and the frequency of B lymphocytes producing anti-HBs antibody was estimated based on the Poisson statistical analysis. The total number of CD19+ B lymphocytes were counted in the peripheral blood of all subjects by flow cytometry. Our results demonstrated a similar precursor frequency of specific B lymphocytes in all subject groups before vaccine administration (< 2 x 10(-5)). Following vaccination, however, a significant increase in the number of specific B lymphocytes was observed in good-responder (1.5 x 10(-4)) and to a lesser extent poor-responder (3.5 x 10(-5)) individuals, but not in non-responders. These findings suggest a defect in either the primary B-cell repertoire or helper T-cell function in non-responder individuals.

Interaction of social and individual learning in food preferences of Norway rats

We conducted four experiments to examine the effects of individual experience of postingestive consequences of eating foods on the longevity of Norway rats', Rattus norvegicus, socially enhanced food preferences. The results of these experiments showed that: (1) waning of a socially enhanced food preference resulted from experience of postingestive consequences of foods, (2) time available each day to sample foods affected the rate at which a socially enhanced food preference waned, (3) the relative value of a food for which enhanced preference had been socially induced and of alternative foods markedly affected the rate at which socially enhanced preferences waned, and (4) experience of a food and its alternatives after social enhancement of a food preference had a significantly greater effect on the rate at which the socially enhanced preference waned than similar exposure to the same foods before social enhancement of a preference. These results are consistent with the view that social learning acts primarily to introduce behaviour into an individual's repertoire and experience of the consequences of engaging in a socially learned behaviour and its alternatives determines the persistence of the socially learned behaviour.

Early phonetic and lexical development: a productivity approach.

Researchers frequently examine the development of the single-word lexicon in the absence of phonetic data. Yet a large body of literature demonstrates relationships between the phonetics of babble and early speech, and it is clear that production skill is essential for establishing a lexicon. This study uses longitudinal productivity criteria to establish children's phonetic skill. Twenty children were followed from age 9 to 16 months, and their level of consistency of vocal patterns was examined in relation to their lexical production, providing a relatively large-sample demonstration of phonetic/lexical relationships at the transition to language. Number of specific consonants produced consistently across the months of observation predicted referential lexical use at 16 months, whereas the transition to reference itself signaled the onset of a sharp increase in numbers of different words produced in a session. The earliest referential speakers exhibited prior consistency in the production of [p/b], which also predominated in their words. Prior use of at least two supraglottal consonants characterized the referential group. Children varied in the specific consonants they produced consistently, and these same consonants, varying according to individual child repertoire, characterized nearly all consonant-based words produced by each child in both of the final 2 months of observation. These findings are interpreted in relation to the children's contemporaneous development of representational ability and pragmatic skill.

Romancing the past: Heritage visiting and the nostalgic consumer

AbstractOver the past decade, there has been growing interest in nostalgia and consumption experiences on the part of a small group of consumer researchers. This article offers an insight into the nostalgic experiences gained through consuming history at a contemporary British “living” museum. The findings of the research focus on two types of nostalgic behavior, which are identified as existential and aesthetic. Differences in the nostalgic reaction are conceptualized in relation to such factors as the quantity and quality of the individual's role repertoire, the experience of alienation in the present, and the extent and quality of social contact. The article aims to offer a perspective that draws upon both existing work in related fields and the findings of the research in order to contextualize nostalgia as an experiential factor behind the consumption of recreated history in the living interactive museum. © 2001 John Wiley &amp; Sons, Inc.