The role of B cells in the induction of peripheral T cell tolerance

Abstract

The immune system of vertebrates is designed to protect against invading pathogens. To be able to deal with different antigenic threats, the T cell repertoire is very diverse. This diversity, though useful, can cause autoimmune diseases if any imbalances in the function of the immune system occur. However, the immune system has its own mechanisms for suppressing or regulating the potentially dangerous, autoreactive T cells. The first mechanism is central tolerance, where potentially self-reactive thymocytes, which encounter APC expressing self-encoded molecules, are triggered to undergo apoptosis so that the thymocytes are clonally deleted in the thymus. However, thymic deletion of self-reactive T cells seems only to affect cells of the highest affinity, and some autoreactive T cells (with low affinity to self-molecules) still manage to gain access to the periphery [1, 2]. Furthermore, only T cells, which recognize antigens expressed within the thymus, are clonally deleted. This means that T cells, which are capable of recognizing tissue-restricted antigens, can still manage to make it to the periphery [2]. To deal with the threat posed by these self-reactive T cells, there are mechanisms for induction of peripheral T cell tolerance. Tolerance can be defined as the state of unresponsiveness to a specific antigen as a result of the presence of one or more mechanisms, which suppress the immune reaction. Thus, tolerance is an active process and is not just the absence of an immune response. B cells are professional APC, which activate or tolerize T cells to help induce or suppress immune responses. There are several mechanisms by which B cells induce tolerization of the T cell compartment. Identifying how peripheral T cell tolerance can be induced will serve to design new therapeutic strategies for regulating the balance between tolerance and active immunity in cases such as autoimmune diseases, tumor immunity, and transplant tolerance.