Increasing evidence indicates direct communication channels exist between the nervous and immune systems. In Cell, Wu et al. show that nociceptor sensory neurons originating in the dorsal root ganglia innervate the spleen along vascular networks to reach B cell zones and promote geminal center responses. Depletion of nociceptor neurons in mice led to reduced numbers of germinal cell B cells and plasmablasts compared with controls after immunization with nitrophenyl (NP)-haptenated antigen. Titers of high-affinity antibodies to NP and antigen-specific memory B cells were also reduced in nociceptor-deficient mice. In addition, specific ablation of left thoracic (T8–T13) TRPV1+ nociceptor neurons resulted in decreased antibody responses after immunization; by contrast, specific activation of these neurons enhanced germinal center responses. Furthermore, the authors show prostaglandin E2 (PGE2)-activated nociceptors release the neuropeptide calcitonin gene-related peptide (CGRP) in response to immunization or after influenza virus infection. CGRP binds to cognate heterodimeric CALCRL–RAMP1 receptors expressed on the surface of germinal center B cells, and exogenous CGRP could rescue the blunted humoral response seen after ablation of the TRPV1+ nociceptor neurons. These findings show that a direct interaction occurs between splenic nociceptor neurons and B cells to enhance humoral immunity.

Original reference: Cell 187, 2935–2951 (2024)