The lymph node revisited: development, morphology, functioning, and role in triggering primary immune responses

Scenarios have been proposed to explain how lymphoid components of a lymph node favor the encounter of a drained antigen with a circulating competent naïve lymphocyte to trigger a primary immune response. However, these scenarios rest on incorrect concepts about the organ. This situation resulted from a loss of interest for studies on in vivo lymphoid organs due to a widespread switch, decades ago, to work on suspended lymphoid cells. However, an in vivo holistic study of the organ continued in our laboratory. The present review synthesizes resulting knowledge on lymph node morphology and global functioning. We show that the opening of an afferent lymphatic vessel into the subcapsular sinus is the focal point from which the related portion of a lymph node-a node compartment-is developed. As to the formation of a compartment's lymphoid components, it is neonatally orchestrated by the dichotomic nature and distribution of antigens in this subcapsular sinus, which determines a dichotomic recruitment of circulating cells and the compartment's architectural complexity. The transport process of an antigen from a given tissue territory into restricted sites of the draining compartment further defines its local morphological features and activities, while providing the possibility to reduce the wandering of a short-lived naïve cell through innumerable target-devoid sites. We also explain that the nodal lymphoid components are not implicated in the triggering of primary responses, but are rather products of such responses. Scenarios for the triggering of primary responses, consistent with real node morphology and functioning, are proposed.