B-cell function

Adenosine deaminase deficiency is associated with an immunodeficiency disease in which both thymus-derived lymphocytes (T cells) and bone marrow-derived lymphocytes (B cells) are sparse and dysfunctional. Purine nucleoside phosphorylase deficiency is associated with a severe deficiency of T cells but apparently normal B cell function. Immune dysfunctions appear to result from accumulation of dGTP and dATP, which inhibit ribonucleotide reductase and thereby deplete cells of DNA precursors. 

The influence of B-cells on disease pathology, and their successful targeting with biologic agents, has stimulated great interest in the discovery of small molecules that modulate B-cell function. Three kinases... 

Depresses T- and B-cell function reduces lymphokines alters macrophage function increases infections... 

Assays such as this that use polyclonal mitogens for activation may not be as sensitive as specific antigen-driven systems (Luster et al., 1988). In addition, suppression of the mitogen response does not always correlate with the PFC response. Since mitogenesis represents only a small aspect of B-cell function and maturation, this endpoint is not sensitive to early events that may affect activation, or later events that may affect differentiation of B cells into antibody-secreting cells (Klaus and Hawrylowicz, 1984). 

Stimulates eosinophil formation stimulates T-cell and B-cell functions... 

The abnormal T- and B-cell functions in patients with SCID are the result of ADA dehciency. The ADA gene has been mapped to chromosome 20q.l3, and a number of point and deletion mutations have been identihed in SCID patients [5-7]. ADA catalyses the irreversible deamination of adenosine and 2 -deoxyadenosine to inosine and 2 -deoxyi-nosine as a part of purine nucleoside metabolism. Adenosine and deoxyadeno-sine are suicide inachvators of S-adenosyl-homocysteine (SAH) hydrolase, and lead indirectly to intracellular accumulation of SAH, which is a potent inhibitor of methy-lation reactions. Cellular methylation function is essential for detoxihcation of adenosine and deoxyadenosine. As a result ADA dehciency leads to accumulation to... 

The conversions of inosine to hypoxanthine (Fig. 25-17, step e), of guanosine to guanine (step g), and of other purine ribonucleosides and deoxyribonucleo-sides to free purine bases are catalyzed by purine nucleoside phosphorylase.318 321b Absence of this enzyme also causes a severe immune deficiency which involves the T cells. However, B cell function is not impaired.312 315 322... 

Dube MP, Edmondson-Melancon H, Qian D, Aqeel R, Johnson D, Buchanan TA. Prospective evaluation of the effect of initiating indinavir-based therapy on insulin sensitivity and B cell function in HIV-infected patients. J Acquir Immune Defic Syndr 2001 27(2) 130-4. 

Langman, R.E. Cohn, M. (1987). The E-T (elephant-tadpole) paradox necessitates the concept of a unit of B-cell function the protecton. Mol. Immunol. 24,675-697. 

Cyclophosphamide s major active metabolite is phosphoramide mustard, which cross-links DNA to prevent cell replication. It suppresses T cell and B cell function by 30-40% the T cell suppression correlates with clinical response in the rheumatic diseases. 

Through regulation of gene transcription, cyclosporine inhibits IL-1 and IL-2 receptor production and secondarily inhibits macrophage-T cell interaction and T cell responsiveness (see Chapter 56 Immunopharmacology). T cell-dependent B cell function is also affected. 

Although this treatment has been available for idiopathic thrombocytopenic purpura for several years, its mechanism of action is not understood. Removal of IgG and IgG-containing immune complexes does not explain its effects in rheumatoid arthritis. The most recent hypothesis for this treatment s mechanism of action is down-regulation of B cell function through the release of small amounts of staphylococcal protein A complexed with immunoglobulins. 

TCDD on B-cell function in vivo have not been examined, in vitro studies suggest that... 

Moreover, since B-cell function is dependent on T-cells, it is uncertain whether these are primary or secondary effects, or both. Thus, supplementation with various vitamin and mineral antioxidants have shown the following (C6, D13, E3, Ml2, P12) ... 

Williams, J. W., Bremer E. G., Finnegan, A. (1996). Regulation of B cell function by the immunosuppressive agent Leflunomide. Transplantation 61, 635-642. 

In the B cell compartment, follicular DCs (FDCs) orchestrate B cell function. Whether FDCs originate from hematopoietic progenitors or from sriomal elements is still a controversy. New evidence suggests the presence of two types of FDCs within the human germinal centers the classic FDCs... 

Antibodies to the Ro(SSA) cellular antigen (244,397) and circulating cryoglobulins (244) are risk factors for adverse reactions to penicillamine. AntiRo (SSA) antibodies characterize a distinct group of patients with rheumatoid arthritis who are almost exclusively female, express more activated B cell function, have a high prevalence of Sjogren s features, and commonly develop adverse reactions to penicillamine. Rashes and febrile reactions were especially associated with anti-Ro(SSA) antibodies, and renal pathology was more frequent in men (244). 

IL-13 is a recently described cytokine secreted by different human T cell subsets and is a potent modulator of human monocyte and B cell function (Minty et al., 1993). Both CDT" and CDB" T cell clones synthesize IL-13 in response to antigen-specific or polyclonal stimuli (Zurawski and De Vries, 1994). IL-13 has profound effects on human monocyte morphology, surface antigen expression, antibody-dependent cellular toxicity and cytokine synthesis (Minty et al., 1993 McKenzie et al., 1993). In human monocytes stimulated by LPS, the production of proinflammatory cytokines, chemokines... 

McKenzie, A.N.J., Culpepper, J.A., de Waal Malefyt, R., Brifcre F., Punnonen J., Aversa G., Sato, A., Dang, W., Cocks, B.G., Menon, S., De Vries, J.E., Banchereau, J. and Zurawski, G. (1993). Interleukin 13, a T-cell-derived cytokine that regulates human monocyte and B-cell function. Proc. Natl. Acad. Sci. USA 90, 3735-3739. 

Recent evidence suggests that there are at least two subpopulations of Th cells, designated Thi and Th2- To date, the distinction between these two populations has been operationally defined and is based on the respective profiles of lymphokines which are produced whereas both Thi and Thi cells produce IL-3 and GM-CSF only Thi cells produce IL-2 and ILN-y, and only Thi cells produce IL-4, IL-5, IL-6, and IL-10. The importance of this phenomenon can be understood from the discussion of the primary effects of these lymphokines. By virtue of the production of IL-2 and ILN-y, Thi cells will facilitate the generation of a cell-mediated immune response. In contrast, Th2 cells will facilitate the generation of a humoral immune response by virtue of producing lymphokines which support B-cell function. Moreover, as indicated in Table 1, Thi cells can downregulate the activity of Th2 cells via the production of ILN-y, and Th2 cells can downregulate the activity of Thi cells via the production of IL-4 and IL-10. The basis for this cross talk between the two types of Th cells has been called the cytokine network. An important outcome of this cytokine network is that under certain conditions, a cell type traditionally characterized as a helper cell can actually suppress an immune... 

IL-1/3 has a potentiating effect on insulin secretion, suggesting a priming effect on B-cell function and also a paracrine effect on A -I- B-cell function. IL-1/3 should be considered to be a physiological modulator of insulin and... 

It is now recognized that the development of Type-II diabetes requires a genetic component which predisposes to the disease, an abnormality in pancreatic B-cell function and the presence of insulin resistance in skeletal muscle, adipose tissue and the liver. Obesity is the most common condition associated with Type-II diabetes by hyperinsulinaemia and insulin resistance. 

There is less consensus with regard to non-insulin-dependent (Type-II) diabetic patients about when to use what medication, and particularly at what point insulin therapy is appropriate. The natural history in obese Type-II diabetes patients usually starts with both impaired B-cell function and insulin resistance and/or basal hyperinsulinaemia resulting in elevated fasting blood glucose levels. 

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