Adrenergic nerves regulate B cell responses to large antigens through modulation of lymph node permeability

Adrenergic nerves innervate all secondary lymphoid organs, although the role of these nerves in adaptive immune responses is unclear. Systemic depletion of these nerves compromises germinal center formation after infection or vaccination. We have found that these nerves locally are required for optimal B cell responses to the large antigen keyhole limpet hemocyanin (KLH), but are dispensable for the B cell response to the small antigen Ovalbumin. After vaccination or infection the reticulin fiber network in the lymph node undergoes remodeling to allow high molecular weight particles, such as KLH, access to the conduit system when they are ordinarily restricted. In contrast, low molecular weight molecules like Ovalbumin always have access to the conduit system. This remodeling of the reticulin fiber network to allow permeability to large molecules was dependent upon the local adrenergic nerves. These findings may help explain why patients with nerve injuries are more likely to have recurrent infections.