Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease that predominant-ly affects the kidneys in the form of lupus nephri-tis, although multiple organs can be involved. Lu-pus nephritis is characterized by the deposition in glomeruli of immune complexes formed by IgG, IgM and IgA autoantibodies (which collectively are called antinuclear antibodies). These autoanti-bodies are directed toward ubiquitous nuclear an-tigens, particularly double-stranded DNA. 1 De-position of these complexes can result in renal failure and even death. Several mechanisms are known to contribute to the pathogenesis of lupus nephritis, including those mediated by type 1 helper T (Th1) and type 17 helper T (Th17) cells. 2 Although humoral re-sponses in the form of autoreactive antibodies (also known as immunoglobulins) are effector mediators of lupus nephritis and the presence of IgE autoantibodies has been reported in some patients, the way in which type 2 helper T (Th2) cells and B cells are activated in the pathogenesis of lupus nephritis has not been clear. Charles and colleagues 3 shed some light on the question through experiments involving mice with " hyperactive " B cells. Specifically, Lyn, a protein tyrosine kinase that negatively regulates B-cell activation, was absent in these mice. Autoim-mune disease developed spontaneously in the mice fairly late in life (at 32 to 40 weeks). This disease shared features with SLE: the mice had anti−double-stranded DNA antibodies, deposition of immune complexes in glomeruli and kidney damage. In additional experiments with other types of knockout mice, Charles et al. concluded that lupuslike nephritis and the production of antinuclear antibodies and anti−double-stranded DNA immunoglobulins in the Lyn-deficient mice were dependent on both interleukin-4 and IgE (Fig. 1), thus suggesting a role for the Th2 envi-ronment. This conclusion shone the spotlight on basophils and mast cells, the two major cell types implicated in Th2-dependent pathogenesis. The authors observed that the induced deficiency of mast cells in the Lyn-deficient mice did not mod-ify the autoimmune process, whereas a depletion of basophils led to markedly reduced numbers of circulating autoreactive IgGs, splenic plasma cells and levels of proinflammatory mediators (such as interleukin-4) in the kidneys. How then would basophils promote lupus ne-phritis? Basophils express Fc$\epsilon$RI (a high-affinity receptor for IgE antibodies), the binding of which (by the IgE immune complex) leads to activation of basophils. Charles et al. found that Lyn-defi-cient mice indeed contained autoreactive IgE and IgE immune complex in the circulation that both mediated the activation of basophils and their homing to secondary lymphoid organs. Through their secretion of interleukin-4 in these organs, the basophils promote Th2 differentiation (Fig. 1). Th2 cells, in cooperation with interleukin-6 and B-cell−activating factor (bound to the basophil Figure 1 (facing page). The Basophil and Lupus Nephritis. Charles et al. 3 recently described a study providing support for a model of pathogenesis of nephritis in systemic lupus erythematosus (SLE). IgE-containing immune complexes in both mice with " hyperactive " B cells (Lyn-deficient mice) and persons with SLE trig-ger circulating basophils to express a secondary lym-phoid organ−homing receptor (CD62L, also known as L-selectin) and the antigen-presenting molecule, ma-jor-histocompatibility-complex (MHC) class II. In sec-ondary lymphoid organs, these activated basophils secrete interleukin-4 and thus promote type 2 helper T (Th2) cell differentiation. Th2 cells — in cooperation with basophil-derived interleukin-6 and basophil mem-brane-bound B-cell−activating factor (BAFF) — enhance B-cell differentiation and survival and produc-tion of autoreactive antibodies. The immune complexes of which these autoreactive antibodies are part are de-posited in glomeruli and cause lupus nephritis.