Abstract
We have previously shown that predominant expression of key inflammatory cytokines and chemokines at autoimmune sites or tumor sites induces loss of B cells tolerance, resulting in autoantibody production against the dominant cytokine/chemokine that is largely expressed at these sites. These autoantibodies are high-affinity neutralizing antibodies. Based on animal models studies, we suggested that they participate in the regulation of cancer and autoimmunity, albeit at the level of their production cannot entirely prevent the development and progression of these diseases. We have, therefore, named this selective breakdown of tolerance as “Beneficial Autoimmunity.” Despite its beneficial outcome, this process is likely to be stochastic and not directed by a deterministic mechanism, and is likely to be associated with the dominant expression of these inflammatory mediators at sites that are partially immune privileged. A recent study conducted on autoimmune regulator-deficient patients reported that in human this type of breakdown of B cell tolerance is T cell dependent. This explains, in part, why the response is highly restricted, and includes high-affinity antibodies. The current mini-review explores this subject from different complementary perspectives. It also discusses three optional translational aspects: amplification of autoantibody production as a therapeutic approach, development of autoantibody based diagnostic tools, and the use of B cells from donors that produce these autoantibodies for the development of high-affinity human monoclonal antibodies.
Highlights
Autoantibodies to self-components are commonly associated with the development of autoimmunity, allergic diseases, and scleroderma [1,2,3,4,5,6]
These results, together with ours may suggest that preferred expression of an inflammatory cytokine/chemokine at an autoimmune site that undergoes a destructive process may induce breakdown of tolerance and generation of autoantibodies to this predominant mediator, and that for anti-CCL3 it might be beneficial for the host
Based on our previous observations and these findings, we suggest a model in which the expression of inflammatory cytokines at sites that are partially segregated from immune surveillance would induce T-dependent loss of B cell tolerance and generation of neutralizing autoantibodies to these inflammatory mediators that are likely to participate in the regulation of cancer and autoimmunity (Figure 1)
Summary
We have previously shown that predominant expression of key inflammatory cytokines and chemokines at autoimmune sites or tumor sites induces loss of B cells tolerance, resulting in autoantibody production against the dominant cytokine/chemokine that is largely expressed at these sites. A recent study conducted on autoimmune regulator-deficient patients reported that in human this type of breakdown of B cell tolerance is T cell dependent This explains, in part, why the response is highly restricted, and includes high-affinity antibodies.
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