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

[Vissen als biomarkers voor immunotoxicologie.]

Abstract niet beschikbaarThis report presents a brief survey on the state of the art in the development and application of biomarkers for immunotoxicology in fish. There are several reasons for developing this field: many fish diseases are related to environmental quality, various environmental pollutants have immunotoxic potential and many fish diseases have an immunological component. As in immunotoxicology in general, in fish this aspect has received ample attention in the recent past. Much benefit has been obtained from progress in related fields of science, such as fish immunology and rodent immunotoxicology. To date there is a broad spectrum of potential biomarkers for immunotoxicology in fish, from which macrophage parameters seem to be most widely used. The application of others and more predictive for specific immunity, such as lymphoid cell parameters is still limited, probably due to practical problems such as lack of experience with conduct, validation and interpretation. Specific problems include the paucity of background data in the case of epidemiological field studies and the important role of other (non-chemical) stress factors in the immune response, and hence the lack of specificity of potential biomarkers. It is concluded that a promising arsenal of biomarkers does exist, but further development and validation are still needed.RIV

Altered marginal zone and innate-like B cells in aged senescence-accelerated SAMP8 mice with defective IgG1 responses

11 páginas, 6 figuras. Contirne información suplementaia en: http://dx.doi.org/10.1038/cddis.2017.351Aging has a strong impact on the activity of the immune system, enhancing susceptibility to pathogens and provoking a predominant pre-inflammatory status, whereas dampening responses to vaccines in humans and mice. Here, we demonstrate a loss of marginal zone B lymphocytes (MZ, CD19+CD45R+CD21++CD23lo) and a decrease of naive B cells (CD19+IgD+), whereas there is an enhancement of a CD19+CD45Rlo innate-like B cell population (B1REL) and the so-called aged B cell compartment (ABC, CD45R+CD21loCD23loCD5-CD11b-) in aged senescence-accelerated (SAMP8) mice but not in aged senescence-resistant (SAMR1) mice. These changes in aged SAMP8 mice were associated with lower IgG isotype levels, displaying low variable gene usage repertoires of the immunoglobulin heavy chain (VH) diversity, with a diminution on IgG1-memory B cells (CD11b-Gr1-CD138-IgM-IgD-CD19+CD38+IgG1+), an increase in T follicular helper (TFH, CD4+CXCR5+PD1+) cell numbers, and an altered MOMA-1 (metallophilic macrophages) band in primary follicles. LPS-mediated IgG1 responses were impaired in the B1REL and ABC cell compartments, both in vitro and in vivo. These data demonstrate the prominent changes to different B cell populations and in structural follicle organization that occur upon aging in SAMP8 mice. These novel results raise new questions regarding the importance of the cellular distribution in the B cell layers, and their effector functions needed to mount a coordinated and effective humoral response.This work was supported by Acción Estratégica de Salud Carlos III (AESI), Grant PI14/0049 and Ministerio de Economía, Industria y Competitividad (MINECO), Grant SAF2015-70880-R, Grant SAF2015-70433-R and BFU 2013-42746.Peer reviewe