Leptin Receptor Deficiency Impairs Lymph Node Development and Adaptive Immune Response.

Activation and clonal expansion of the Ag-specific adaptive immune response in the draining lymph node is essential to clearing influenza A virus infections. Activation sufficient for virus clearance is dependent on the lymph node's architectural organization that is maintained by stromal cells, chiefly fibroblastic reticular cells. During an analysis of influenza A virus clearance in leptin receptor knockout (DB/DB) mice, we observed that the DB/DB mice have markedly reduced numbers of lymph node fibroblastic reticular cells at the steady state. The reduction in lymph node fibroblastic reticular cells resulted in abnormal lymph node organization and diminished numbers of adaptive immune cells in the lymph nodes under homeostatic conditions. As a consequence, the DB/DB mice were impaired in their ability to generate an effective influenza-specific adaptive immune response, which prevented virus clearance. Using leptin receptor mutant mice with point mutations at distinct signaling sites in the leptin receptor, we were able to link the leptin receptor's signaling domain tyrosine 985, which does not contribute to obesity, to lymph node fibroblastic reticular cell development and function. These results demonstrate a novel role for leptin receptor signaling in regulating lymph node development in a manner that is crucial to the generation of Ag-specific adaptive immune responses.

B cells going viral in the CNS: Dynamics, complexities, and functions of B cells responding to viral encephalitis.

A diverse number of DNA and RNA viruses have the potential to invade the central nervous system (CNS), causing inflammation and injury to cells that have a limited capacity for repair and regeneration. While rare, viral encephalitis in humans is often fatal and survivors commonly suffer from permanent neurological sequelae including seizures. Established treatment options are extremely limited, predominantly relying on vaccines, antivirals, or supportive care. Many viral CNS infections are characterized by the presence of antiviral antibodies in the cerebral spinal fluid (CSF), indicating local maintenance of protective antibody secreting cells. However, the mechanisms maintaining these humoral responses are poorly characterized. Furthermore, while both viral and autoimmune encephalitis are associated with the recruitment of diverse B cell subsets to the CNS, their protective and pathogenic roles aside from antibody production are just beginning to be understood. This review will focus on the relevance of B cell responses to viral CNS infections, with an emphasis on the importance of intrathecal immunity and the potential contribution to autoimmunity. Specifically, it will summarize the newest data characterizing B cell activation, differentiation, migration, and localization in clinical samples as well as experimental models of acute and persistent viral encephalitis.