Skin Deep and Beyond: Unravelling B Cell Extracellular Matrix Interactions in Cutaneous Immunity and Disease

The extracellular matrix (ECM) is a crucial component in multicellular organisms, serving as both a structural scaffold and active signalling units. While the role of the ECM, namely, to maintain homeostasis and steer adaptive immunity, is well described in secondary lymphoid organs, it is underappreciated in the skin-despite remarkable molecular similarity. Here, we examine how the specialised organisation of the ECM influences B cell development and function in both skin and secondary lymphoid organs with a special focus on ECM-integrin signalling. We discuss the presence and function of B cells in healthy and diseased skin, including their role in wound healing, autoimmune responses and inflammatory conditions. Additionally, we explore the formation of tertiary lymphoid structures in chronic skin diseases as a window into studying B cell-ECM interactions. By integrating fundamental immunology with skin biology, we aim to identify key knowledge gaps and explore potential clinical implications of B cell-ECM interactions in dermatology and beyond.