Overview

In autoimmune diseases, the body no longer tolerates some of its own tissues, and its B cells regard those tissues, cells, or proteins as if they were foreign invaders and attack them by producing antibodies. The consequences of this autoantibody production can be devastating. In lupus, antibodies to double-stranded DNA can damage, and even destroy, the kidney.

B cells

The human body produces millions of uniquely different B cells, each with the potential to recognize and eliminate a different invading antigen, such as those found on a bacterium or virus. An antigen is any substance that causes your immune system to produce antibodies against it. Antibodies are produced by your body in response to substances that are perceived as a threat or harmful. Each B cell produces antibodies against a specific molecular structure on the antigen's surface. Rather than targeting bacteria, viruses or other antigens, occasionally B cells incorrectly identify certain body cells or proteins as foreign.

When functioning properly, the immune system distinguishes between its own tissues and foreign antigens. The two fundamental immune responses, antibody-mediated and cell-mediated, are controlled by two types of white blood cells, B cells and T cells, respectively. T cells primarily help to rid the body of cells that have become infected or cancerous. B cells provide antibody-mediated immunity that helps to eliminate circulating infectious agents and other antigens.

B cells produce antibodies that recognize and bind to antigens and mark them for destruction. Each B cell type makes only one kind of antibody. An antibody binds to a specific structure on an antigen's surface called an epitope. The B cell also displays this antibody on its membrane as a receptor for the antigen.

Tolerizing B cells

B cells are normally triggered to produce antibodies by a two-step process. After B cells encounter an antigen, these partially activated B cells migrate through the lymphoid tissue. If an activated B cell encounters a T cell that has been activated by the same antigen, antibodies against that antigen are produced. If the B cell does not receive a required signal from a corresponding T cell, it will become inactive or die.

Immune tolerance is a natural mechanism that is designed to eliminate development of B cells that target "self," rather than foreign antigens. La Jolla Pharmaceutical Company employs the concept of B cell tolerance to make proprietary Toleragens®, molecules which are engineered to kill or inactivate pathogenic B cells that produce antibodies to "self." Toleragens are designed to deliver a specific and potent B cell signal, but not a T cell signal. Thus, binding of a Toleragen to a specific B cell is thought to stop production of pathogenic antibodies and to cause the cell to die or become inactive. That is, the B cell has become "tolerized" to a particular antigen.

Toleragens are composed of multiple copies of B cell epitopes attached to a non-immunogenic carrier platform. The same basic, non-immunogenic carrier platform approach is designed to be used with different epitopes to make a variety of Toleragens to treat a variety of autoimmune diseases.

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