B cell tolerance

Fan X, Tyerman K, Ang A, et al. A novel tool for B-cell tolerance research characterization of mouse alloantibody development using a simple and reliable cellular ELISA technique. Transplant. Proc. 2005 37 29-31. 

Klinman, N.R. (1996). The clonal selection hypothesis and current concepts of B cell tolerance. Immunity 5, 189-195. 

Abnormal B cell tolerance Abnormal central deletion... 

Figure 2. Four mechanisms to achieve B cell tolerance. B cells with an auto-reactive BCR can (i) be driven into apoptosis, (ii) undergo receptor editing of the Ig LC, (iii) dilute out the self-reactive BCR by co-expression of an innocuous conventional LC, or (iv) become anergic.

In addition to the observed defect in central B cell silencing, deletion of peripheral autoreactive and polyreactive B cells is clearly defective. In fact, in most RA patients no significant decline in the fraction of autoreactive or polyreactive B cells has been observed during transitional B cell differentiation. In conclusion, both a defect at central and peripheral B cell tolerance contributes to the increased fraction of autoreactive and polyreactive mature B cells in RA patients. 

Yurasov, S., H. Wardemann, J. Hammersen, M. Tsuiji, E. Meffre, V. Pascual, and M. C. Nussenzweig. 2005. Defective B cell tolerance checkpoints in systemic lupus erythematosus. The Journal of experimental medicine 201 703-711. 

Samuels, J., Y. S. Ng, C. Coupillaud, D. Paget, and E. Meffre. 2005. Impaired early B cell tolerance in patients with rheumatoid arthritis. The Journal of experimental medicine 201 1659-1667. 

Stadanlick, J. E., and M. P. Cancro. 2008. BAFF and the plasticity of peripheral B cell tolerance. Current opinion in immunology 20 158-161. 

There are two mechanisms by which therapeutic proteins induce antibodies the classical activation of the immune system by foreign proteins and the breaking of B cell tolerance by human proteins. The two mechanisms differ in time of onset and response level as we have described extensively previously [2]- Also the immunological mechanisms behind the two types of immune activation differ fundamentally and therefore also the characteristics of the product that are involved in induction of antibodies. 

Spontaneous human autoimmunity seems to be almost entirely restricted to the autoantibody responses produced by B-lymphocytes. Loss of tolerance by T-ceUs has been extremely hard to demonstrate, and where there is evidence for an abnormal T-ceU response it is usually not to the antigen recognised by the autoantibody. This disparity has led to the idea that human autoimmune disease is in most cases (with probable exceptions including type I diabetes) based on a loss of B-cell tolerance, which makes use of normal T-cell responses to foreign antigens in a variety of aberrant ways. 

Figure 6.4-1. Schematic representation of a possible mechanism of breaking B-cell tolerance. The antigen contains multiple epitopes that cross-link B-cell receptors. The cross-linking of the receptors is observed as a danger signal because of which the B cells start to proliferate to plasma cells and produce antibodies.

Fazekas de St Groth. B. (1998) Namre Versus Nurture Contributions of Developmental Programming and the Microenvironmental to B Cell Tolerance, Immunol. Cell Biol. 76,369-372. 

Mitchell GF, Humphrey JH, Williamson AR (1972) B cell tolerance induced by polymeric antigens I. Comparison of the dose and epitope density requirements for inactivation of primed and unprimed B cells in vivo. Eur J Immunol 5 361 Mota I (1964) The mechanism of anaphylaxis I. Production and biological properties of mast cell sensitizing antibody. Immunology 7 681 Neftel KA Waelti M Spengler H Von Felten A Weitzman SA Buergi H de Week AL (1981) Neutropenia after penicillins Toxic or immune-mediated Klin Wochenschr 59 877... 

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