B-lymphocytes, innate immunity, and autoimmunity

[Guest guest]

B-lymphocytes, innate immunity, and autoimmunity

Muriel Viau and Moncef ZoualiCorresponding Author Contact Information,

E-mail The Corresponding Author

Institut National de Santé et de Recherche Médicale (INSERM U 430),

Immunopathologie Humaine, 75006 Paris, France

Received 18 June 2004; accepted 30 August 2004. Available online 5

November 2004.

Abstract

Having evolved to generate a huge Ag-specific repertoire and to mount T

cell-dependent responses and long-term memory, the B lymphocyte is a central

player in the adaptive branch of immune defense. However, accumulating

evidence indicates that B-1 cells of the peritoneal cavity and marginal zone

(MZ) B cells of the spleen also can play innate-like immune functions. Their

anatomical locations allow frequent Ag encounter. Secreting essentially

germline-encoded, polyreactive Abs, and responding rapidly and vigorously to

stimulation, these two B cell subsets have evolved to impart potentially

protective responses. With their additional capacities to secrete factors

that can directly mediate microbial destruction and to express Toll-like

receptors (TLR), B cells provide an important link between the innate and

adaptive branches of the immune system.

Currently, the relevance of these innate-like B cells to the pathogenesis of

autoimmune disease is the focus of investigation. In experimental models of

autoimmunity, the sequestration of autoreactive B cells in the MZ has been

proposed to be essential for the maintenance of self-tolerance. The low

activation threshold of MZ B cells makes them particularly reactive to high

loads and/or altered self-Ags, potentially exacerbating autoimmune disease.

Their expansion in autoimmune models and their association with autoantibody

secretion indicate that they may participate in tissue damage. The

demonstration that B cell depletion therapies may represent a highly

beneficial therapeutic goal in autoimmune disorders suggests that specific

elimination of B-1 and MZ B cells may represent a more efficient

immunointervention strategy in systemic autoimmunity.