Immunization Elicits Antigen-Specific Antibody Sequestration in Dorsal Root Ganglia Sensory Neurons

Abstract

The immune and nervous systems are two major organ systems responsible for host defense and memory. Both systems achieve memory and learning that can be retained, retrieved, and utilized for decades. Here, we report the surprising discovery that peripheral sensory neurons of the dorsal root ganglia (DRGs) of immunized mice contain antigen-specific antibodies. Using a combination of rigorous molecular genetic analyses, transgenic mice, and adoptive transfer experiments, we demonstrate that DRGs do not synthesize these antigen-specific antibodies, but rather sequester primarily IgG1 subtype antibodies. As revealed by RNA-seq and targeted quantitative PCR (qPCR), dorsal root ganglion (DRG) sensory neurons harvested from either naïve or immunized mice lack enzymes (i.e., RAG1, RAG2, AID, or UNG) required for generating antibody diversity and, therefore, cannot make antibodies. Additionally, transgenic mice that express a reporter fluorescent protein under the control of Igγ1 constant region fail to express Ighg1 transcripts in DRG sensory neurons. Furthermore, neural sequestration of antibodies occurs in mice rendered deficient in neuronal Rag2, but antibody sequestration is not observed in DRG sensory neurons isolated from mice that lack mature B cells [e.g., Rag1 knock out (KO) or μMT mice]. Finally, adoptive transfer of Rag1-deficient bone marrow (BM) into wild-type (WT) mice or WT BM into Rag1 KO mice revealed that antibody sequestration was observed in DRG sensory neurons of chimeric mice with WT BM but not with Rag1-deficient BM. Together, these results indicate that DRG sensory neurons sequester and retain antigen-specific antibodies released by antibody-secreting plasma cells. Coupling this work with previous studies implicating DRG sensory neurons in regulating antigen trafficking during immunization raises the interesting possibility that the nervous system collaborates with the immune system to regulate antigen-mediated responses.

Changes in the transcriptional fingerprint of satellite glial cells following peripheral nerve injury

“…Heatmap showing the expression in individual samples normalized to the maximum expression value for each gene. References: SGC markers (Berger & Hediger, ; Li et al, ; Procacci et al, ; Vit et al, ; Weick et al, ), Schwann cell markers (Gao et al, ; Krekoski, Neubauer, Graham, & Muir, ; Richner et al, ; Ryu et al, ), neuronal markers (Gunasekaran et al, ; Han et al, ; Richner et al, ; Ruscheweyh, Forsthuber, Schoffnegger, & Sandkühler, ) and immune cell markers (Chen et al, ; Nakano, Harada, Morikawa, & Kato, ; Strauss‐Ayali, Conrad, & Mosser, ; Tomlinson et al, )…”

The Role of Antibodies and Their Receptors in Protection Against Ordered Protein Assembly in Neurodegeneration

“…The discrepancies between these findings may lie in the region of the brain analyzed as staining has been reported to be specific to regional neuron populations (66) or may reflect ex vivo vs. in vivo conditions. Outside the brain, FcγRI expression has been detected on sensory and motor neurons (67–69). TRIM21 is universally expressed and we have confirmed its expression in mouse primary neurons and human neuroblastoma cells (70).…”

Profiling of how nociceptor neurons detect danger – new and old foes

“…More recently, dorsal root ganglia were found not to synthesize the antigen‐specific antibodies found in peripheral sensory neurons, but rather sequester primarily IgG 1 subtype antibodies. Thus, dorsal root ganglion sensory neurons harvested from either naïve or immunized mice lack the enzymes RAG1, RAG2, AID and UNG, which are necessary to produce these various antibodies and failed to express Ighg1 transcripts in DRG sensory neurons . Whilst the role and consequences of neuronal sequestration of IgG1 remain unclear, it may serve as a local pool of releasable antigen‐specific antibody .…”