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a Inserm U606, Université Paris 7, F-75475 Paris Cedex 10, France
Key Words: superantigen • S. aureus protein A • P. magnus protein L • HIV-1 gp120 • B cell repertoire • innate immunity • B-1a cells • marginal zone cells • autoimmunity
Address for correspondence: Moncef Zouali, Inserm U606, Centre Viggo Petersen, Hôpital Lariboisière, 2, rue Ambroise Paré, F-75475 Paris Cedex 10, France. Voice: +33-1-49-95-63-28; fax: +33-1-45-84-79-62. e-mail: moncef.zouali{at}wanadoo.fr
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.
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