Many diseases are characterized by pathogenic autoantibodies such as hemolytic anemia (erythroctye surface antigen), graves’ disease (thyroid stimulating hormone R).

There are several ways to deal with autoreactive immature B cells in BM.

clonal deletion: This involves deletion and editing in the bone marrow.

receptor editing: change their receptor to become non-self reactive. If cell is successful in receptor editing, it can move to periphery. Otherwise cell dies. Receptor editing is a mechanism to eliminate self reactive B cells upon encounter with strong self antigen. About 1/4 of the cells of immature B cells undergo receptor editing.

anergy: make the cells unresponsive to antigen and short lived. Chronically exposure to antigen results in reduced ability to signal. When a tolerant B cell encounters a CD4+ T cells, will not behave properly. It can trigger a TCR but not good at inducing other molecules. However, multivalent foreign antigen (stronger antigens) can still activate anergic B cells.

Competitive elimination: of autoreactive B cells in the periphery. Elimination is promoted by the pro-apoptotic BH3-only molecule Bim, a bcl-2 antagonist.