B-cell development : one problem, multiple solutions.

Interspecies variations in the processes of B-cell development and repertoire generation contrast with the greater consistency of T-cell development. B-cell development in mice and humans, with postnatal B-cell generation of new repertoire in the bone marrow throughout life, is regarded as the 'standard' pattern. In contrast, accounts of B cells in birds, sheep, cattle, rabbits and pigs (the 'other' species) describe cessation of gene diversification in the perinatal period, with the gut-associated lymphoid tissue (GALT) functioning as the primary lymphoid organ thereafter. It has become customary to regard the developmental pathways of T and B cells within any individual species as being as dissimilar as the functions of the two mature cell types. Reinterpretation of B-cell development patterns in different species is overdue in response to two types of reports. The first of these describe T-B 'crossover', specifically the intrathymic production of B cells and the extrathymic production of T cells. The second attests to the extent of sharing of B-cell developmental features across the two groups of species. We propose that, as is a feature of other haematopoietic cells, a menu of alternative B- and T-cell pathways has been retained and shared across species. A single pathway usually predominates in any species, masking alternatives. The observed predominance of any pathway is determined by factors such as placental permeability, extent of maturation of the immune system by birth and the feasibility of direct experimental intervention in development

Toxicity and cellular uptake of gold nanoparticles: what we have learned so far?

Gold nanoparticles have attracted enormous scientific and technological interest due to their ease of synthesis, chemical stability, and unique optical properties. Proof-of-concept studies demonstrate their biomedical applications in chemical sensing, biological imaging, drug delivery, and cancer treatment. Knowledge about their potential toxicity and health impact is essential before these nanomaterials can be used in real clinical settings. Furthermore, the underlying interactions of these nanomaterials with physiological fluids is a key feature of understanding their biological impact, and these interactions can perhaps be exploited to mitigate unwanted toxic effects. In this Perspective we discuss recent results that address the toxicity of gold nanoparticles both in vitro and in vivo, and we provide some experimental recommendations for future research at the interface of nanotechnology and biological systems

EVOLUTION OF ANTIGEN BINDING RECEPTORS

This review addresses issues related to the evolution of the complex multigene families of antigen binding receptors that function in adaptive immunity. Advances in molecular genetic technology now permit the study of immunoglobulin (Ig) and T cell receptor (TCR) genes in many species that are not commonly studied yet represent critical branch points in vertebrate phylogeny. Both Ig and TCR genes have been defined in most of the major lineages of jawed vertebrates, including the cartilaginous fishes, which represent the most phylogenetically divergent jawed vertebrate group relative to the mammals. Ig genes in cartilaginous fish are encoded by multiple individual loci that each contain rearranging segmental elements and constant regions. In some loci, segmental elements are joined in the germline, i.e. they do not undergo genetic rearrangement. Other major differences in Ig gene organization and the mechanisms of somatic diversification have occurred throughout vertebrate evolution. However, relating these changes to adaptive immune function in lower vertebrates is challenging. TCR genes exhibit greater sequence diversity in individual segmental elements than is found in Ig genes but have undergone fewer changes in gene organization, isotype diversity, and mechanisms of diversification. As of yet, homologous forms of antigen binding receptors have not been identified in jawless vertebrates; however, acquisition of large amounts of structural data for the antigen binding receptors that are found in a variety of jawed vertebrates has defined shared characteristics that provide unique insight into the distant origins of the rearranging gene systems and their relationships to both adaptive and innate recognition processes

Camelid Ig V genes reveal significant human homology not seen in therapeutic target genes, providing for a powerful therapeutic antibody platform

International audienceno abstrac

Early Vλ diversification in sheep

This study examined a number of tissues during early gestation in foetal sheep to determine the earliest site of Vλ expression and time of generation of the Vλ repertoire. Tissues, including spleen, liver, gut, blood and bone marrow, were obtained from 48, 55, 60 and 63 gestational day (g.d.) ovine foetuses and cDNA libraries were prepared from them by reverse transcription–polymerase chain reaction. Clones were randomly selected from cDNA libraries and subjected to sequencing. Analysis of these sequences and comparison with a pool of germline genes led to the following conclusions. The expression of Vλ occurs earlier in spleen (48 g.d.) than in all of the other tissues examined. Also, diversity is seen earlier and at higher levels in early foetal spleen than in all of the other tissues examined. In this regard, it is notable that splenic Vλ expression is readily apparent even before such gut-associated lymphoid tissue as the ileal Peyer's patch (IPP) has developed. Two germline Vλ genes, 5.1 and 5.3 predominate in early immunoglobulin λ light-chain gene rearrangement. Examination of Jλ usage revealed the existence of a new Jλ gene and its utilization during the early phases of the development of the ovine antibody repertoire. This study indicates that sites other than the IPP contribute to the diversification of the Vλ repertoire in sheep. We suggest that it is likely that foetal spleen may provide a partially diversified B-cell repertoire before the IPP becomes active as a major site for massive clonal expansion and extensive diversification of B cells