21:T4d0,Natural antibodies contribute to tissue homeostasis and protect against infections. They are secreted constitutively without external antigenic stimulation. The differentiation state and regulatory pathways that enable continuous natural antibody production by B-1 cells, the main cellular source in mice, remain incompletely understood. Here we demonstrate that natural IgM-secreting B-1 cells in the spleen and bone marrow are heterogeneous, consisting of (a) terminally differentiated B-1-derived plasma cells expressing the transcriptional regulator of differentiation, Blimp-1, (b) Blimp-1⁺, and (c) Blimp-1^neg phenotypic B-1 cells. Blimp-1^neg IgM-secreting B-1 cells are not simply intermediates of cellular differentiation. Instead, they secrete similar amounts of IgM in wild-type and Blimp-1-deficient (PRDM-1^ΔEx1A) mice. Blimp-1^neg B-1 cells are also a major source of IgG3. Consequently, deletion of Blimp-1 changes neither serum IgG3 levels nor the amount of IgG3 secreted per cell. Thus, the pool of natural antibody-secreting B-1 cells is heterogeneous and contains a distinct subset of cells that do not use Blimp-1 for initiation or maximal antibody secretion.22:T4d4,Using a new biaxial friction apparatus, we conducted experiments of ice-on-rock friction in order to better understand basal sliding of glaciers and ice streams. A series of velocity-stepping and slide-hold-slide tests were conducted to measure friction and healing at temperatures between -20°C and melting. Experimental conditions in this study are comparable to subglacial temperatures, sliding rates and effective pressures of Antarctic ice streams and other glaciers, with load-point velocities ranging from 0.5 to 100 µm s^-1 and normal stress σ_n= 100 kPa. In this range of conditions, temperature dependences of both steady-state friction and frictional healing are considerable. The friction increases linearly with decreasing temperature (temperature weakening) from μ = 0.52 at -20°C to μ = 0.02 at melting. Frictional healing increases and velocity dependence shifts from velocity-strengthening to velocity-weakening behaviour with decreasing temperature. Our results indicate that the strength and stability of glaciers and ice streams may change considerably over the range of temperatures typically found at the ice-bed interface.This article is part of the themed issue 'Microdynamics of ice'.23:T449,B-1a cells play an important role in mediating tissue homeostasis and protecting against infections. They are the main producers of 'natural' IgM, spontaneously secreted serum antibodies predominately reactive to self antigens, like phosphatidylcholine (PtC), or antigens expressed by the intestinal microbiota. The mechanisms that regulate the B-1a immunoglobulin (Ig) repertoire and their antibody secretion remain poorly understood. Here, we use a novel reporter mouse to demonstrate that production of self- and microbiota-reactive antibodies is linked to BCR signaling in B-1a cells. Moreover, we show that Toll-like receptors (TLRs) are critical for shaping the Ig repertoire of B-1a cells as well as regulating their antibody production. Strikingly, we find that both the colonization of a microbiota as well as microbial-sensing TLRs are required for anti-microbiota B-1a responses, whereas nucleic-acid sensing TLRs are required for anti-PtC responses, demonstrating that linked activation of BCR and TLRs controls steady state B-1a responses to both self and microbiota-derived antigens.24:T45c,Evolutionarily conserved, "natural" (n)IgM is broadly reactive to both self and foreign antigens. Its selective deficiency leads to increases in autoimmune diseases and infections. In mice, nIgM is secreted independent of microbial exposure to bone marrow (BM) and spleen B-1 cell-derived plasma cells (B-1PC), generating the majority of nIgM, or by B-1 cells that remain non-terminally differentiated (B-1sec). Thus, it has been assumed that the nIgM repertoire is broadly reflective of the reperto

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