B Cell Receptor Signaling in Human Systemic Lupus Erythematosus

Aimee E. Pugh-Bernard; John C. Cambier

Disclosures

Curr Opin Rheumatol. 2006;18(5):451-455. 

In This Article

Antibody-Independent Function of B Cells in Systemic Lupus Erythematosus

Although the exact role of B cells in SLE is not completely understood, the use of a mouse model that completely lacked B cells revealed that the presence of B cells is critical to the development of SLE.[13,14] An MRL/lpr mouse containing B cells that expressed membrane-bound IgM but lacked exons needed for secretion was produced (mIgM.MRL/Mp-Faslpr) in an attempt to clearly distinguish the role of B cells as antibody secreting or antigen-presenting cells.[15] The resulting mice possessed B cells, but no circulating antibodies, yet still exhibited classic signs of autoimmunity, including T cell activation, cellular infiltration and increased mortality.[15] This clearly demonstrated a critical role for B cells in the pathogenesis of disease aside from the secretion of autoantibody. Further, the association of spontaneous T cell activation with disease supports the idea that B cells act as (auto)antigen-presenting cells in the promotion of autoimmune disease as B cell-deficient MRL/lpr mice, that produce functional dendritic cells and macrophages, exhibit markedly reduced numbers of spontaneously activated and memory CD4+ T cells.[13,14,16]

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