The B cell activating factor BAFF (BlyS/TALL-1/zTNF4) is a tumor necrosis factor (TNF)-related ligand that promotes B cell survival and binds to three receptors (BCMA, TACI, and the recently described BAFF-R). Here we report an absolute requirement for BAFF in normal B cell development. Examination of secondary lymphoid organs from BAFF-deficient mice revealed an almost complete loss of follicular and marginal zone B lymphocytes. In contrast, mice lacking BCMA had normal-appearing B lymphocyte compartments. BAFF therefore plays a crucial role in B cell development and can function through receptors other than BCMA.

Background and Purpose-The present study was performed to determine the role of ␣4 (CD49d), a member of the integrin family of adhesion molecules, in ischemic brain pathology. Methods-Male spontaneously hypertensive rats (SHR) or Sprague-Dawley rats underwent 60-minute middle cerebral artery occlusion (MCAO) followed by 23-hour reperfusion. Animals were injected intravenously with 2.5 mg/kg anti-rat ␣4 antibody (TA-2) or isotype control antibody (anti-human LFA-3 IgG 1 , 1E6) 24 hours before MCAO. Infarct volume was quantified by staining of fresh tissue with tetrazolium chloride and myeloperoxidase activity measured in SHR tissue homogenates 24 hours after MCAO. In SHR, mean arterial blood pressure was recorded before and after MCAO in animals treated with TA-2 and 1E6. Fluorescence-activated cell sorting analysis was performed on peripheral blood leukocytes before and after MCAO. Results-TA-2 treatment significantly reduced total infarct volume by 57.7% in normotensive rats (1E6, 84.2Ϯ11.5 mm 3 , nϭ17; TA-2, 35.7Ϯ5.9 mm 3 , nϭ16) and 35.5% in hypertensive rats (1E6, 146.6Ϯ15.5 mm 3 , nϭ15; TA-2, 94.4Ϯ25.8 mm 3 , nϭ11). In both strains, TA-2 treatment significantly reduced body weight loss and attenuated the hyperthermic response to MCAO. In SHR, treatment with TA-2 significantly reduced brain myeloperoxidase activity. Resting mean arterial blood pressure was unaffected by treatment. Leukocyte counts were elevated in TA-2-treated rats. Fluorescence-activated cell sorting analysis demonstrated the ability of TA-2 to bind to CD3ϩ, CD4ϩ, CD8ϩ, and CD11bϩ cells in both naive animals and after MCAO.Conclusions-These data demonstrate that inhibition of ␣4 integrin can protect the brain against ischemic brain injury and implicate endogenous ␣4 integrin in the pathogenesis of acute brain injury. The mechanism by which ␣4 integrin inhibition offers cerebroprotection is independent of blood pressure modulation and is likely due to inhibition of leukocyte function.

The tight skin 1 (B6.CgFbn1(Tsk)+/+Pldn(pa)/J, henceforth referred to as Tsk1/+) mouse was first described as a spontaneously occurring mutant that resulted in hyperplasia of the subcutaneous loose connective tissue, and has subsequently been proposed to be a model of the human fibrotic disorder scleroderma. We have investigated the Tsk1/+ mouse as a model system for testing the efficacy of antifibrotic agents against skin fibrosis. We find that the tightness of the skin at the scruff of the neck leads to a measurably thicker skin pinch, but we suggest that this is due to hyperplasia of the subdermal loose connective tissue, which results in increased tethering of the skin to the underlying muscle layers. In contrast to previously published data, we do not find a significant difference in the dermal thickness or collagen content of the Tsk1/+ mouse skin compared with wild-type controls. In addition, expression profiling of Tsk1/+ mouse skin indicated that there are very few changes in gene expression, and that there is no evidence for upregulation of the transforming growth factor beta signaling axis. Therefore, we conclude that this model is not suitable for testing the effect of antifibrotic agents on the dermis, and that changes potentially related to scleroderma may be confined to subdermal connective tissue.