ROLE OF BREGS & TREGS IN AUTOIMMUNITY

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ROLE OF TREGS AND BREGS IN AUTOIMMUNITY

For years, the roles of lymphocytes in the immune system have concentrated on T cell specialization. Regulatory T cells, commonly known as Tregs, dial down immune attacks and fight autoimmune diseases. They are used to treat everything from allergies, organ rejection, to cancer.

Recently other lymphatic cells, B cells, appear to share with Tregs, the responsibility for keeping the immune system under control. These lymphocytic regulatory T cells, have been named Bregs, and release anti-inflammatory molecules that can forestall autoimmunity. Researchers are wondering which B cells are regulators, what triggers them to assume that role, and how these beta B cells can influence the immune system.

There is debate over the origin of regulatory T cells--whether they are different from the start or change because of environmental conditions. There is no consensus on what role Bregs plays in autoimmune disorders and cancer. These cells, however, may help strengthen immunity to attacks on diseases, as lupus and multiple sclerosis.

Most people think of B cells as antibodies. After a bacteria infiltrates the body, mature B. cells recognize the bacteria, and turns itself into plasma cells. Over their two-week lifespan, they produce bacterial fighting proteins. These Beta cells now have been found to also serve as antigens presenting cells, showing molecular bits of the attacking bacteria to other immune cells. Thus, the B cells help initiate a counterattack on these microbes.

In the past, scientists were convinced that cytokines, chemical messengers for the immune system, released by B. cells had little impact on other cells. These B. cells however determine whether help comes from specialized T cells that fight bacteria and viruses. Their B. cell cytokines arouse the immune system.

These cells come in multiple varieties sporting a unique combination of protein markers on its surface. One set of B. cells produce IL-10, which alleviates auto immune conditions. Other B. cells that can't manufacture IL--10 had no effect on autoimmunity.

Beta-10 cells have been isolated from lymphocytes and are found in one to 3% of the beta cells in the spleen. These B-10 cells, which are regulatory beta cells, account for almost all of the IL--10 released by beta cells. Injecting the B10 cells into inflamed joints reduced joint damage, and when injected into healthy cartilage, blocked autoimmune responses.

The question is: Which antigens if any, are necessary to put Bregs into action? Mature B. cells mobilize in response to particular antigens. When you have the flu, only matured B. cells with surface bound antibody receptors that match the flu virus’s protein will attack the virus. The Beta cell then transforms into a plasma cell that then secrete large quantities of antibodies.

What drives a B. cell to become regulatory, instead of becoming merely a plasma cell? It's possible that any B. cell could become a regulatory T cell. The decisive signal for the cell to change, comes through Toll like receptors (TLRs). TLRs are proteins on the surface of some body's cells that detect pathogen molecules. TLR activation is necessary if a beta cell is going become regulatory. Stimulation of certain TLR proteins turn a B. cell into a regulatory B cell.

Some spleen cells started becoming B-10 cells, but become functional IL--10 releasers, only after being prodded by molecules from other immune cells or pathogens.

COMMENTARY

Researchers are looking for different ways to put B. cells into action. They are now using doses of the antibody rituximab to treat rheumatoid arthritis and lupus.

The therapy knocks out ALL beta cells in the body. But, since they remove all the bad cells and good cells together, failure has resulted. They are now looking for cell surface markers on the beta cells not found on other T cells, to target only the bad B. cells. Evidence suggests that beta cells can abet cancer. B. cells often infiltrate tumors and are drawn into tumors by chemicals secreted by the cancer cells as they try to fight off immune attacks.

The most famous beta cell product, antibodies, has a role in immunity. Important questions still must be answered on the role of Bregs and Tregs in producing autoimmunity in humans.

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Sources: Science, July 10,2009 /Science, Nov. 23, 2007/ Science, Aug 6,2004