title: Emerging concepts regarding B cells and autoantibodies in murine lupus nephritis. B cells have multiple roles; all autoantibodies are not equal.
abstract: Despite observations linking the severity of lupus nephritis to the quantity and location of glomerular immune deposits, it had been difficult to decipher the primary role of B cells and autoantibodies in this process. Newer technologies have provided the means to evaluate the roles of whole B cell populations and individual immunoglobulins in lupus lesions. In this review, recent advances in this area are summarized, with particular emphasis on work from the authors' laboratories. The results implicate a primary role for B cells and immunoglobulins in lupus nephritis, including glomerular, interstitial, and vascular lesions. Multiple antibody-ligand interactions participate in glomerular immune deposit formation in individuals with lupus nephritis. Recent evidence suggests that in situ formation of immune deposits by either cross-reactivity of autoantibodies with intrinsic glomerular antigens (i.e., anti-DNA antibodies with laminin) or direct interaction of autoantibodies with circulating autoantigens lodged within glomeruli (i.e., anti-DNA antibodies with histone/DNA). The predominant autoantibody-glomerular antigen interaction(s) in a given individual influences the principal location of immune deposition, which in turn influences the pathologic and clinical expression of disease. It is believed that these phenomena contribute to the phenotypic diversity commonly observed among individuals with lupus nephritis. Furthermore, these consequences are dependent on properties unique to both subsets of lupus autoantibodies and to their target antigen ligands within the glomerulus. Thus, the autoantibody variable or antigen binding region, along with the nature and location of the target glomerular antigen (or site of circulating antigen deposition), are influential in initiating these perturbations.
authors.forename: M P
authors.initials: MP
authors.lastname: Madaio
authors.forename: M J
authors.initials: MJ
authors.lastname: Shlomchik
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology*; D001665:Binding Sites; D008181:Lupus Nephritis / Q000209:etiology / Q000276:immunology / Q000503:physiopathology*; D051379:Mice
chemical_list: D001323:Autoantibodies