Biology subjects

Spillane, K. M.

Publications and source records attributed to Spillane, K. M..

3 recordsLinked to original sources

bioRxiv2024

Antigen mobility regulates the dynamics and precision of antigen capture in the B cell immune synapse

B cells discriminate antigens in immune synapses by capturing them from antigen-presenting cells. This discrimination relies on the application of mechanical force to B cell receptor (BCR)-antigen bonds, allowing B cells to selectively disrupt low-affinity interactions while internalizing high-affinity antigens. Using DNA-based tension sensors combined with high-resolution imaging, we demonstrate that the magnitude, location, and timing of forces within the immune synapse are influenced by the fluidity of the antigen-presenting membrane. Transitioning antigens from a high-mobility to a low-mobility substrate significantly increases the probability and speed of antigen extraction while also improving affinity discrimination. This shift in antigen mobility also reshapes the synapse architecture, altering spatial patterns of antigen uptake. Despite these adaptations, B cells maintain consistent levels of proximal and downstream signaling pathway activation regardless of antigen mobility. They also efficiently transport internalized antigens to major histocompatibility complex class II (MHCII)-positive compartments for processing. These results demonstrate that B cells mount effective responses to antigens across diverse physical environments, though the characteristics of that environment may influence the speed and accuracy of B cell adaptation during an immune response.

immunology↗

bioRxiv2022

Subcapsular sinus macrophage sensing of extracellular matrix rigidity alters membrane topography and immune complex mobility

Subcapsular sinus macrophages (SSMs) play a key role in immune defence by forming immunological barriers that control the transport of pathogens from lymph into lymph node follicles. SSMs participate in antibody responses by presenting antigens directly to naive B cells and by supplying antigens to follicular dendritic cells to propagate germinal centre reactions. Despite the prominent roles that SSMs play during immune responses, little is known about their cell biology because they are technically challenging to isolate and study in vitro. Here, we used multi-colour fluorescence microscopy to identify lymph nodederived SSMs in culture. We focused on the role of SSMs as antigen-presenting cells and found that their actin cytoskeleton regulates the spatial organisation and mobility of immune complexes displayed on the cell surface. Moreover, we determined that SSMs are mechanosensitive cells that respond to changes in extracellular matrix (ECM) rigidity by altering the architecture of the actin cytoskeleton, leading to changes in cell morphology, membrane topography, and immune complex mobility. Our results reveal a new mechanism regulating physical aspects of antigen presentation by antigen-presenting cells, which may have implications for B cell activation and antibody responses.

immunology↗

bioRxiv2022

Long-term retention of antigens in germinal centres is controlled by the spatial organisation of the follicular dendritic cell network

Germinal centers (GCs) require sustained availability of antigens to promote antibody affinity maturation against pathogens and vaccines. A key source of antigens for GC B cells are immune complexes (ICs) displayed on follicular dendritic cells (FDCs). Here we show that FDC spatial organization regulates antigen dynamics in the GC. We show the existence of two light zone (LZ) FDC populations, which differ in the duration of antigen retention. While the entire light zone (LZ) FDC network captures ICs initially, only the central cells of the network function as a long-term antigen reservoir, where different antigens arriving from subsequent immunizations co-localize. Mechanistically, central FDCs constitutively express subtly higher CR2 membrane densities than peripheral FDCs, which strongly increases the IC retention half-life. Even though repeated immunizations gradually saturate central FDCs, B cell responses remain efficient because new antigens partially displace old ones. These results reveal the principles shaping antigen display on FDCs during the GC reaction.

immunology↗