The natural history of defences

Hosts can avoid infections by behavioural changes and by body walls. After infection, hosts can change their behaviours to reduce the effects of parasitism. Immune defences have different arms (humoral or cellular), and organization (innate, adaptive). Innate immunity consists of a collection of different systems that are evolutionarily very old. Adaptive immunity, based on expansion of specific lymphocytes, evolved in the higher vertebrates. Immune defences are regulated tightly and based on receptors that can recognize parasites (or their activity). This triggers a complex signalling cascade that results in the production of further signalling compounds and effectors. Important protein families, e.g. the immunoglobulins, form the molecular backbone. A key to efficient defences is the diversification of receptors, such as the highly evolved somatic diversification processes of advanced adaptive immunity. The microbiota adds to defences in many ways. Immune memory and priming occur throughout the tree of life.

DETECTION OF SELECTION SIGNALS IN CATTLE POPULATIONS BY PCA

The presented study provides a genome-wide scan of selection signals in cattle by principal component analysis (PCA). The aim was to identify SNP affected by intensive selection based on package PCAdapt implemented under software R. This analysis provided insight into the association between the SNP frequencies related to population differentiation. The four cattle populations were involved in the analysis (Slovak Spotted cattle, Ayrshire, Swiss Simmental and Holstein) with overall 272 of genotyped individuals. After applying quality control, the final dataset consisted of 35 675 SNPs, with an overall length of 2496.14 Mb and average space between adjacent SNP 70.03 ± 76.1 kb. After performing PCA analysis, the uniqueness of the breeds was revealed. On the other hand, a close genetic relationship and eleven SNPs affected by selection were found, with a position close to 162 genes involved in the various biological processes. The majority of genes were involved in the positive regulation of adenylate cyclase activity, embryo development and somatic diversification of immune receptors via somatic mutation. Several candidate genes for genetic control of the immune system (DNAJB9), muscle development (SEPT7, TRIM32, ROCK1, NRAP, PZDZ8, HSPA12A and FGFR2), milk production (SOCS5, CD46), reproduction (LHCGR, EEPD1, FSHR) and coat colour (KIT) were identified. Our results provide insights into the regions of the genome affected by the intensive selection of analysed cattle populations.

The immunogenetics of sexual parasitism

Sexual parasitism has evolved as a unique mode of reproduction among deep-sea anglerfishes. The permanent attachment of males to host females observed in these species represents a form of anatomical joining, which is otherwise unknown in nature. Striking modifications to immune facilities are associated with this reproductive trait. The genomes of species with temporarily attaching males lack functional aicda genes that underpin affinity maturation of antibodies. Permanent attachment is associated with additional alterations, culminating in the loss of functional rag genes in some species, abolishing somatic diversification of antigen receptor genes, the hallmark of canonical adaptive immunity. In anglerfishes, co-evolution of innate and adaptive immunity has been disentangled, implying that an alternative form of immunity supported the emergence of this evolutionarily successful group of vertebrates.

Cytidine deaminase 2 is required for VLRB antibody gene assembly in lampreys

The antibodies of jawless vertebrates consist of leucine-rich repeat arrays encoded by somatically assembled VLRB genes. It is unknown how the incomplete germline VLRB loci are converted into functional antibody genes during B lymphocyte development in lampreys. In Lampetra planeri larvae lacking the cytidine deaminase CDA2 gene, VLRB assembly fails, whereas the T lineage–associated VLRA and VLRC antigen receptor gene assemblies occur normally. Thus, CDA2 acts in a B cell lineage–specific fashion to support the somatic diversification of VLRB antibody genes. CDA2 is closely related to activation-induced cytidine deaminase (AID), which is essential for the elaboration of immunoglobulin gene repertoires in jawed vertebrates. Our results thus identify a convergent mechanism of antigen receptor gene assembly and diversification that independently evolved in the two sister branches of vertebrates.

Evolution of Alternative Adaptive Immune Systems in Vertebrates

Adaptive immunity in jawless fishes is based on antigen recognition by three types of variable lymphocyte receptors (VLRs) composed of variable leucine-rich repeats, which are differentially expressed by two T-like lymphocyte lineages and one B-like lymphocyte lineage. The T-like cells express either VLRAs or VLRCs of yet undefined antigen specificity, whereas the VLRB antibodies secreted by B-like cells bind proteinaceous and carbohydrate antigens. The incomplete VLR germline genes are assembled into functional units by a gene conversion–like mechanism that employs flanking variable leucine-rich repeat sequences as templates in association with lineage-specific expression of cytidine deaminases. B-like cells develop in the hematopoietic typhlosole and kidneys, whereas T-like cells develop in the thymoid, a thymus-equivalent region at the gill fold tips. Thus, the dichotomy between T-like and B-like cells and the presence of dedicated lymphopoietic tissues emerge as ancestral vertebrate features, whereas the somatic diversification of structurally distinct antigen receptor genes evolved independently in jawless and jawed vertebrates.

Somatic diversification in the absence of antigen-driven responses is the hallmark of the IgM+IgD+CD27+ B cell repertoire in infants

T cell–dependent immune responses develop soon after birth, whereas it takes 2 yr for humans to develop T cell–independent responses. We used this dissociation to analyze the repertoire diversification of IgM+IgD+CD27+ B cells (also known as “IgM memory” B cells), comparing these cells with switched B cells in children <2 yr of age, with the aim of determining whether these two subsets are developmentally related. We show that the repertoire of IgM+IgD+CD27+ B cells in the spleen and blood displays no sign of antigen-driven activation and expansion on H-CDR3 spectratyping, despite the many antigenic challenges provided by childhood vaccinations. This repertoire differed markedly from those of switched B cells and splenic germinal center B cells, even at the early stage of differentiation associated with μ heavy chain expression. These data provide evidence for the developmental diversification of IgM+IgD+CD27+ B cells, at least in very young children, outside of T cell–dependent and –independent immune responses.