T and B cell Antigen Receptors

There are at least six different Stat proteins, from which it can be assumed that these are phosphorylated with differing efficacy by the various receptor tyrosine kinases. In addition, expression of Stat proteins is cell and tissue specific. 

At the DNA level, variability of the DNA elements specific for Stat proteins and accessibility of the promoter sites are further determining factors for specificity of signal transduction. 

At the surface of T and B lymphocytes, specific receptors are found that bind antigens and set intracellular signal chains in motion (review Weiss and Littman, 1994 Paul and Seder, 1994 Qian and Weiss, 1997). These may lead to increased cell division, programmed cell death or a functional recoining of lymphocytes. 

The receptors of the B lymphocytes recognize antigens in the form of foreign proteins, which exist in soluble, particle-boimd or cell-boimd forms. 

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The unique domain following the SH4 domain from the N-terminus is a region with considerable variation in the amino acid sequences among different Src family members. This unique domain may be involved in protein-protein interactions. For example, the unique region of Lck is linked to CD4 and CD8, while those of Fyn and Lyn may be associated with the T- and B-cell antigen receptors. 

The T and B cell antigen receptors are generally composed of several subunits, whereby the frmctions of ligand binding and conduction of the signal are localized on separate subrmits (review Weiss and Littman, 1994 Wilson and Garcia, 1997). 

Intracellular Signal Molecules of the T and B Cell Antigen Receptors... 

The T and B cell antigen receptors do not have any intrinsic protein tyrosine kinase activity. Rather, antigen binding leads to recruitment and activation of protein tyrosine kinases on the cytoplasmic side of the receptor. Probably, coupling of the tyrosine kinase takes place via the ARAM motif directly. 

R. Zhang, F. W. Alt, L. Davidson, S. H. Orkin, and W. Swat. Defective signalling fhrou the T- and B-cell antigen receptors in lymphoid cells lacking the vav proto-oncogene. Nature, 374 (6521), 470-473, 1995. 

Hochstenbach, F., David, V., Watkins, S, and Brenner, M. B. (1992). Endoplasmic reticulum resident protein of 90 kilodaltons associates with the T- and B-cell antigen receptors and major histocompatibility complex antigens during their assembly. Proc. Natl. Acad. Sci USA 89, 4734-4738. 

Cambier, J.C., 1992, Signal transduction by T- and B-cell antigen receptors converging structures and concepts, Current Opinion Immunol. 4 257-264. 

A decline in immune response is almost a concomitant of the aging process in animals and in humans, with the most significant effect on ceU-mediated immunity, through a decrease in the number of T lymphocytes and also changes in T ceU surface receptors. The effects of pyridoxine supplanents on lymphocyte responses in elderly persons were studied. Lymphocyte proliferative response to both T and B cell antigens were reduced, and lymphocytes subpopulations were angmented in the vitamin Bg-supplemented group and correlated with plasma PLP levels (84). 

The NHR contains also the conserved Calcineurin docking site, PxlxIT, required for the physical interaction of NEAT and Calcineurin. Dephosphorylation of at least 13 serines residues in the NHR induces a conformational change that exposes the nuclear localization sequences (NLS), allowing the nuclear translocation of NEAT. Rephosphorylation of these residues unmasks the nuclear export sequences that direct transport back to the cytoplasm. Engagement of receptors such as the antigen receptors in T and B cells is coupled to phospholipase C activation and subsequent production of inositol triphosphate. Increased levels of inositol triphosphate lead to the initial release of intracellular stores of calcium. This early increase of calcium induces opening of the plasma membrane calcium-released-activated-calcium (CRAC) channels,... 

Idiotypic network. Idiotypic determinants (idiotypes) are unique antigenic epitopes characteristic of the antigen receptors on the surface of T and B cells. They are associated with the variable regions of these receptors. Antibodies produced by B cells as the result of antigenic stimulation can themselves stimulate the production of auto-anti-idiotypic antibodies which have the ability to combine with the B-cell receptor (Ig) and thus can dampen down the immune response. Idiotypes may likewise stimulate the production of T cells specific for idiotypic determinants. Jerne (1974) postulated his... 

Sugawara H, Kurosaki M, Takata M, Kurosaki T 1997 Genetic evidence for involvement of type 1, type 2 and type 3 inositol 1,4,5-trisphosphate receptors in signal transduction through the B-cell antigen receptor. EMBO J 16 3078-3088... 

Saxton, T.M., Oostween, I., BowteU, D., Aebersold R., and Gold, M.R., 1994, B cell antigen receptor crosshnking induces phosphorylation of the ras activators SHC and mSOSl as well as the assembly of complexes containing SHC, Grb2 and SOSl and a 145 kDa tyrosine phosphorylated protein. J. Immunol. 153 623-636. 

Yankee, T. M., L. M. Keshvara, S. Sawasdikosol, M. L. Harrison, and R. L. Geahlen. Inhibition of signaling through the B cell antigen receptor by the protooncogene product, c-Cbl, requires Syk tyrosine 317 and the c-Cbl phosphotyrosine-binding domain. J Immunol. 163 5827-35.1999. 

Both the nonspecific and specific components of the immune system can be suppressed by chemicals, including drugs. It involves the suppression of maturation and development of immune cells. Both T and B cells develop in the bone marrow and thymus. This involves a complex series of changes in relation to antigen receptors and recognition. Chemicals can affect these processes, leading to a decrease in the number of mature T and B cells. This will result in inhibition of both the humoral and cellular responses. 

Poque, S.L., Kurosaki, T., Bolen, J., Herbst, R., 2000, B cell antigen receptor-induced activation of Akt promotes B cell survival and is dependent on Syk kinase. J. Immunol. 

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