A de la Hera

The Participation of B Cells and Antibodies in the Selection and Maintenance of T Cell Repertoires

The imtnune system (IS) of vertebrates is endowed with obvious cognitive properties: it learns, remembers, and makes discriminatory inferences about molecular profiles. Typically, properties of this nature cannot be ascribed to individual components in the system (in our case, to the presence or activity of given clones), but they emerge as global behaviors from its general organization. Immune self/ nonself discrimination is, thus, a characteristically dispersed property of the IS (Varela et al. 1987). It follows that, to understand self/nonself discrimination, we have to be concerned at least as much v̂ fith such global behaviors and distributed properties as with individual clonal specificities. Distributed properties require connectivity between the elements of the system, and of these with other self components. Therefore, we believe, the understanding of self/nonself discrimination must start from the consideration of self-directed reactivities, in clear contrast with the classical notion that immune self/nonself discrimination is based upon the elimination of self-reactive clones (Vaz et al. 1984. Coutinho et al. 1984). Clearly, and this is also the case for conventional points of view, the behavior of an IS at any point in life can only be understood in the context of its own history in the ontogenic development of the individual. Snapshots of adult immune systems based on the study of lymphocyte repertoires, while necessary to realize the structure of the systems components and to construct the anatomy of interactions, will always tell us little about history and overall organization. We must therefore make explicit here the limitations of an approach (clonal

IMMUNOLOGICAL CONSEQUENCES OF HIV INFECTION: ADVANTAGE OF BEING LOW RESPONDER CASTS DOUBTS ON VACCINE DEVELOPMENT

Immunosuppression in AIDS might be due to the immune response rather than to the pathogenicity of the virus. The basis of the immunosuppression could be molecular mimicries involving viral gp-110, CD4 molecules, antibodies, and CD4-acceptor sites. Whether an individual develops auto-immunosuppressive responses or mounts a harmless defence against (or coexists with) the virus follows the general rules of lymphocyte repertoire selection. MHC and V region genes and other polymorphic loci, together with the previous state of the immune system, particularly at early developmental periods, are factors that influence the response. Vaccination against gp 110-HIV might thus protect against infection but at the same time cause auto-immunosuppression and disease.

Modification of Emerging Repertoires by Immunosuppression in Immunodeficient Mice Results in Autoimmunity

One of the fundamental paradigms in immunology has been that the Immune System does not react against the soma and every theory which has attempted to explain the immune response has had to account for the lack of autoreactivity. In those cases where responses to self have been clearly demonstrated, these have been termed autoimmune disease. Yet with 80 years of this paradigm behind us, we have slipped into a new era in which the paradigm has been reversed and reactions against self are used to explain both the initiation and regulation of the immune response. Thus, autoreactivity to major histocompatibility complex (MHC) products is necessary to generate an immune response (the ZinkernagelDoherty-Shearer phenomenon; Moller 1978) and anti-idiotypic interactions may play a crucial role in the regulation of the immune system (Jerne 1974, Moller 1984, 1986). Furthermore, we have recently extended self-recognition within the polymorphic structures (Immunoglobulins (Igs), T-cell receptors (TCR) and MHC antigens) to all other components of the internal environment that have been incorporated into self to an immunosomatic perspective (Vaz et al. 1984). In fact, a large body of evidence has been accumulated in the past indicating the existence of immune reactivity directed toward self-components, as a result of the natural internal activity of the Immune System {Coutinho et al. 1985). Such

Loss of lineage antigens is a common feature of apoptotic lymphocytes

The analysis of apoptosis in cell populations involves the detection of their specific lineage antigen (LAg) expression. This experimental approach relies on their assumed constant expression, but it is unclear whether such expression is actually maintained during cell death. We examined whether the loss of LAgs is a common feature of apoptotic lymphocytes and whether some might completely lose their LAgs. The changes in the expression of CD3, CD5, CD8, CD4, CD28, CD56, and CD19 were monitored in highly purified lymphocyte populations obtained by negative selection in a fluorescence‐activated cell sorter. These were cultured for 24 h with or without phytohemagglutinin or staurosporin. For each LAg‐positive subset studied, apoptosis was consistently more common among cells showing partial or total loss of LAg expression compared with cells maintaining their initial LAg levels. The kinetics of expression loss was rapid for CD8, CD56, and CD28, and more than 80% of initial expression was lost in the early stages of apoptosis but was slower for CD3, CD5, and CD4. For CD3 and CD5, expression was dependent on the apoptotic stimulus used. It is interesting that loss of antigen expression was independent of cell size. This phenomenon was also found in nonmanipulated, highly pure CD19 B lymphocytes of peripheral blood mononuclear cells from B chronic lymphocytic leukemia patients. Loss of LAg expression appeared to be a common feature of apoptotic lymphocytes under all the conditions assayed. The different kinetic patterns of LAg loss suggest apoptotic cells might actively regulate this process.

A Hypothesis for the Selection of Available Repertoires: T‐Cell Network Early in the Intrathymic Differentiation

T‐cell recognition requires direct cell‐cell interactions mediated by major histocompatibility complex (MHC)‐restricted α‐β heterodimeric receptors (Ti) in association with a constant protein complex termed T3 (TcR, Ti‐T3). Interleukin 2 (IL‐2) promotes growth and maturation of T cells upon binding to high affinity receptors (IL2‐R). They are expressed after the recognition of antigen on accessory cells through the TcR [44]. Furthermore, current hypotheses propose that T‐cell interactions are also mediated by a group of T‐cell antigens, particularly T4/L3T4 and T8/Lyt 2 [35], and perhaps Tγ [15]. All their encoding genes are rearranged and/or expressed sequentially during thymocyte differentiation [5, 8, 40, 41, 46, 51, 52]. Thus, developmental analyses of T‐cell function are essential to gain insight into the mechanisms for selection of available repertoires, one of the central problems in immunology.

Meics, a novel zinc-finger protein which relocates from nuclei to the central meiotic spindle during Drosophila spermatogenesis.

A Drosophila gene encoding a novel zinc-finger protein, Meics, was cloned using a monoclonal antibody. The predicted amino acid sequence contains 12 zinc-finger motifs of the C2H2-type. During spermatogenesis, Meics distributes intranuclearly at pre- and post-meiotic stages whereas it relocates to central-spindle microtubules at both meiotic divisions.