Subduction and Slab Detachment Under Moving Trenches During Ongoing India-Asia Convergence

The dynamics of slab detachment and associated geological fingerprints have been inferred from various numerical and analog models. These invariably use a setup with slab-pull-driven convergence in which a slab detaches below a mantle-stationary trench after the arrest of plate convergence due to arrival of continental lithosphere. In contrast, geological reconstructions show that post-detachment plate convergence is common and that trenches and sutures are rarely mantle-stationary during detachment. Here, we identify the more realistic kinematic context of slab detachment using the example of the India-Asia convergent system. We first show that only the India and Himalayas slabs (from India's northern margin) and the Carlsberg slab (from the western margin) unequivocally detached from Indian lithosphere. Several other slabs below the Indian Ocean do not require a Neotethyan origin and may be of Mesotethys and Paleotethys origin. Additionally, the still-connected slabs are being dragged together with the Indian plate forward (Hindu Kush) or sideways (Burma, Chaman) through the mantle. We show that Indian slab detachment occurred at moving trenches during ongoing plate convergence, providing more realistic geodynamic conditions for use in future numerical and analog experiments. We identify that the actively detaching Hindu Kush slab is a type-example of this setting, whilst a 25–13 Ma phase of shallow detachment of the Himalayas slab, here reconstructed from plate kinematics and tomography, agrees well with independent, published geological estimates from the Himalayas orogen of slab detachment. The Sulaiman Ranges of Pakistan may hold the geological signatures of detachment of the laterally dragged Carlsberg slab

Expression of FcRL4 defines a pro-inflammatory, RANKL-producing B cell subset in rheumatoid arthritis

OBJECTIVES: The success of B cell targeting therapies has highlighted the importance of B cells in rheumatoid arthritis pathogenesis. We have previously shown that B cells in the RA synovium are capable of producing pro-inflammatory and bone-destructive cytokines including RANKL. Here we sought to characterise the nature and functional relevance of the RANKL-producing B cell subset in the RA synovium. METHODS: Synovial fluid and peripheral blood B cells from patients with RA were analysed by flow cytometry for markers of B cell differentiation and activation and for chemokine receptors. FcRL4(+) and FcRL4(−) B cells sorted from synovial fluid were analysed for cytokine expression using Taqman low-density arrays. Synovial tissue biopsies obtained from patients with RA were analysed by immunofluorescence for CD20, RANKL and FcRL4. FCRL4 mRNA expression was determined in synovial tissue of RA patients and non-inflammatory control subjects by real-time PCR. RESULTS: RANKL-producing B cells in RA synovial tissue and fluid were identified as belonging to a distinct subset of B cells defined by expression of the transmembrane protein FcRL4. FcRL4+ B cells express a distinct combination of cytokines and surface proteins indicating a function distinct from that of FcRL4− B cells. Notably, FcRL4+ B cells expressed high levels of TNF-α and RANKL mRNA. CONCLUSIONS: We have identified a novel pro-inflammatory B cell population in the RA synovium which is defined by expression of FcRL4 and responsible for RANKL production. This B cell population expresses high levels of CD20, and its removal by rituximab may contribute to the anti-inflammatory effect of this drug