Clonal development

Clonal development of life means condensation of pieces of memory from a pool of limited volume until enough functions can be read from the nucleic acids core to support autonomy. A smooth transition of complex chemistry to complex biochemistry must proceed through stable (immortal) steps and products that last until the next... 

Nomura S, Esumi H, Job C, et al. Lineage and clonal development of gastric glands. Dev Biol 1998 204 124-135. 

Hepatocellular carcinoma (HCC) develops in patients with chronic liver diseases associated with hepatitis B and hepatitis C vims infections with high incidences. Here, an acyclic retinoid has been shown to suppress the posttherapeutic recurrence after interferon-y or glycerrhicin treatment in cirrhotic patients who underwent curative treatment of preceding tumors. The retinoid induced the disappearance of serum lectin-reactive a-fetoprotein (AFP-L3), a tumor marker indicating the presence of unrecognizable tumors in the remnant liver, suggesting a deletion of such minute (pre)malignant clones (clonal deletion). As a molecular mechanism of the clonal deletion, a novel mechanism of... 

Mast cells express high-affinity IgE Fc receptors (FceRI) on their surface, contain cytoplasmic granules which are major sources of histamine and other inflammatory mediators, and are activated to release and generate these mediators by IgE-dependent and non-IgE-dependent mechanisms [1]. Disturbances either in the release of mast cell mediators or in mast cell proliferation are associated with clonal mast cell disorders including monoclonal mast cell activation syndrome (MMAS) and mastocytosis respectively, which are in turn associated with some cases of anaphylaxis [2], Molecular mechanisms have been identified which may link increased releasability of mast cell mediators and conditions leading to increased mast cell numbers [3]. Patients with mastocytosis have an increased risk to develop anaphylaxis [4, 5] and those with anaphylaxis may suffer from unrecognized mastocytosis or may display incomplete features of the disease [6-8]. 

Clonal deletion. Contact with antigen in the neonate results in death or permanent inactivation of the developing lymphocytes. 

Temple S, Raff MC 1986 Clonal analysis of oligodendrocyte development in culture evidence for a developmental clock that counts cell divisions. Cell 44 773-779 Walters SN, Morell P 1981 Effects of altered thyroid states on myelinogenesis. J Neurochem 36 1792-1801... 

Some xenobiotics may have divergent mechanisms of autoimmune responses. For example, hydralazine demonstrates adduct reactivity as well as inhibition of DNA methylation [68,73], while procainamide inhibits DNA methylation, forms immunogenic NPA, and disrupts clonal selection in the thymus [68, 72, 74], It is this complicated pattern of effects that makes assessment of autoimmune potential in the laboratory for new xenobiotics almost impossible. Animal models can sometimes be recreated to resemble human disease [74], and thus may be useful for therapy considerations, but are difficult to utilize for screening chemicals for hazard potential due to the diverse nature of autoimmunity mechanisms and physiological presentation. While evidence supports many different mechanisms for xenobiotic-induced autoimmune reactions, none have conclusively demonstrated the critical events necessary to lead to the development of autoimmune disease. Therefore, it is difficult to predict or identify xenobiotics that might possess the potential to elicit autoimmune disorders. 

Figure 1.7. Lymphocyte activation. When naive lymphocytes first encounter the antigen that is recognised by their receptor, they are stimulated to differentiate and proliferate. This clonal expansion is aided by the production of cytokines. Two cell types develop from this process the effector cells (i.e. either antibody-secreting plasma cells or cytotoxic T cells) and memory cells. Both cell types possess virtually the same receptor that was expressed on the naive lymphocyte.

In conclusion the present report confirms the significant impact of y-retroviral vector insertion sites on the establishment of clonal dominance in hematopoiesis after (serial) bone marrow transplantation. The identification of a number of putative sternness genes may contribute not only to a better understanding of stem cell biology but, in the long run also to the development of novel approaches for stem cell based therapeutic regimens, e.g. in regenerative medicine. 

Although this study provided insight into the clonal composition of human HSC hierarchy, it was unknown if the ex vivo manipulations required for retroviral marking had quantitative or qualitative effects on SRC fates. The developments in lentivector transduction protocols enabled efficient transduction of SRC in the absence of cytokine and serum stimulation . Using minimal ex vivo manipulation to mark hematopoietic cells with lentiviral integration, the fates of SRC were evaluated . As reported previously using retroviral-marking, lentivector transduced short-term SRC contributed rapidly... 

In any battle, when the defence is outnumbered by the enemy, more troops are brought into the battle from the reserve. However, in the immune system, there are initially no reserve troops. When an antigen binds to its complementary antibody-receptor on B-cells, these are strongly stimulated to proliferate (clonal expansion). In addition, not only does the number of daughter cells increase but each quickly develops into what is known as an effector (or plasma) cell, in which the protein synthetic machinery increases through the development of the rough endoplasmic reticulum, so that there is a large increase in the number of antibodies synthesised and secreted. A simple description of the sequence of events is as follows ... 

This is explained by the fact that the lymphocytes that respond to antigens during development are eliminated by apoptosis, a process known as clonal deletion. The lymphocytes subsequently present in the foetus will respond only to foreign proteins, for example, those in a graft from another person which then leads to its rejection. Not surprisingly, the system is more complicated than this. The MHC proteins are required to help the lymphocytes differentiate between self and non-self proteins and much of the antigenic difference between individuals lies in the MHC-class II protein. 

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