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Summary: B cell activating factor (BAFF) provides B cells with essential survival signals. It binds to three receptors: BAFFR, TACI, and BCMA that are differentially expressed by B cell subsets. BAFFR is early expressed in circulating B cells and provides key signals for further maturation. Here, we report that highly regulated BAFFR processing events modulate BAFF responses. BAFFR processing is triggered by BAFF binding in B cells co-expressing TACI and it is executed by the metalloproteases ADAM10 and ADAM17. The degree of BAFF oligomerization, the expression of ADAM proteins in different B cell subsets, and the activation status of the cell determine the proteases involved in BAFFR processing. Inhibition of ADAM10 augments BAFF-dependent survival of primary human B cells, whereas inhibition of ADAM17 increases BAFFR expression levels on germinal center B cells. Therefore, BAFF-induced processing of BAFFR regulates BAFF-mediated B cell responses in a TACI-dependent manner. : Smulski et al. report that the B cell survival receptor BAFFR undergoes ligand-induced shedding but only in cells co-expressing a second receptor for BAFF called TACI. BAFFR shedding can be performed by ADAM10 in circulating B cells or by ADAM17 in germinal center B cells and limits BAFF-mediated survival signals. Keywords: B cell, BAFF-receptor, BAFFR, TACI, ADAM10, ADAM17, metalloprotease, processing, ectodomain shedding, germinal center, survival

T-regulatory cells (Tregs) are essential for immune tolerance, and animal studies implicate their dysfunction in type 1 diabetes (T1D) pathogenesis. Tregs require interleukin-2 (IL-2) for their suppressive function, and variants in IL-2/IL-2R pathway genes have been associated with T1D. We previously reported that recent-onset T1D subjects have an increased population of FOXP3lo Tregs that secrete the pro-inflammatory cytokine, interleukin-17 (IL-17). We hypothesize that IL-2 signaling defects may drive T1D development by skewing protective Tregs towards an inflammatory Th17 phenotype. Overall, we found that the proportion of FOXP3+IL-17+ cells in T1D subjects pre-diagnosis was unchanged compared with healthy controls. However, stratification by IL2RA single-nucleotide polymorphisms revealed that T1D subjects with the rs3118470 CC risk variant have Tregs with IL-2 signaling defects and an increased proportion of FOXP3+IL-17+ cells before diagnosis. These data suggest a potential mechanism for genetically controlled loss of Treg function via dysfunctional IL-2 signaling in T1D.

We conducted an amphibian inventory at Okefenokee National Wildlife Refuge from August 2000 to June 2002 as part of the U.S. Department of the Interior's national Amphibian Research and Monitoring Initiative. Nineteen species of amphibians (15 anurans and 4 caudates) were documented within the Refuge, including one protected species, the Gopher Frog Rana capito. We also collected 1 y of monitoring data for amphibian populations and incorporated the results into the inventory. Detection probabilities and site occupancy estimates for four species, the Pinewoods Treefrog (Hyla femoralis), Pig Frog (Rana grylio), Southern Leopard Frog (R. sphenocephala) and Carpenter Frog (R. virgatipes) are presented here. Detection probabilities observed in this study indicate that spring and summer surveys offer the best opportunity to detect these species in the Refuge. Results of the inventory suggest that substantial changes may have occurred in the amphibian fauna within and adjacent to the swamp. However, mon...

A 78 kDa protein was induced in cat peripheral blood mononuclear cells after in vivo administration of recombinant human interferon-alpha hybrid (rHuIFN-alpha B/D). This protein was antigenically related to the IFN-induced human (78 kDa) and mouse Mx proteins. Quantitative immunoblot analysis indicated that the induction of the cat Mx protein was dose-dependent. There was a dissociation in time between plasma levels of IFN which were transient, and levels of cat Mx protein which remained elevated at least five days after dosing. Our results provide evidence that a human IFN-alpha hybrid may be active in cats. They also indicate that the Mx protein is a sensitive, quantitative, and stable marker to follow IFN activity in vivo in cats.