Exploitation of Host Signaling Pathways by B Cell Superantigens—Potential Strategies for Developing Targeted Therapies in Systemic Autoimmunity

:  Some infectious agents produce molecules capable of interacting specifically with the immunoglobulin heavy‐ or light‐chain variable regions, independently of the conventional‐binding site. They are referred to as B cell superantigens (SAgs) and include protein A of Staphylococcus aureus (S. aureus) , gp120 of HIV‐1, and protein L of Peptostreptococcus magnus (P. magnus) . In contrast to conventional antigens, B cell superantigens interact with conserved framework regions of immunoglobulins and can target a large proportion of B cells. In experimental models, they have been demonstrated to deplete B cell subsets responsible for innate functions, namely B‐1a and marginal zone (MZ) B cells. As a result, the interactions of these superantigens with host cells impair the humoral immune response. In addition to providing clues toward understanding host–pathogen interactions and microbial pathogenesis, B cell superantigens represent potential therapeutic agents that could be used to specifically modulate expansion of B cell subsets in diseased subjects. In systemic autoimmune diseases, for example, there is activation and expansion of B cells that secrete pathogenic autoantibodies. Their depletion results in clinical improvement in both experimental animals and patients. Currently, attempts are being made to specifically deplete pathogenic autoantibody‐producing B cells. Since B‐1a and MZ B cells have been found to be expanded in autoimmune disorders, B cell superantigens, used alone or in combination with other biological agents, may have beneficial effects in autoimmune disease management.