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

Abstract

Subcapsular sinus macrophages (SSMs) play a key role in antibody responses by presenting antigens directly to naive B cells and supplying antigens to follicular dendritic cells to propagate germinal centre reactions. However, 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 node-derived 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 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.

Proteomic profiling of isolated immune synapses from primary mouse B cells

“…Although B cells strongly respond to soluble antigens, in vivo antibody responses are suggested to be more commonly triggered by the binding of foreign, unprocessed antigens on the surface of antigenpresenting cells (APCs) (Batista & Harwood, 2009;Kuokkanen et al, 2015;Shaheen et al, 2019). Different cells can act as APCs for B cells, including subcapsular sinus macrophages (Carrasco & Batista, 2007;Iliopoulou et al, 2022), dendritic cells, and follicular dendritic cells (Heath et al, 2019;Martinez-Riano et al, 2022;Qi et al, 2006;Suzuki et al, 2009). Upon antigen recognition, the interaction between the APC and the B lymphocyte triggers the formation of an activation platform termed immune synapse (IS) (Batista & Harwood, 2009), that serves as critical hub for cellular events linked to BCR signalling and lowers the threshold for receptor activation (Carrasco & Batista, 2007, Natkanski et al, 2013.…”