PT - JOURNAL ARTICLE AU - Louis Scheurer AU - Rebecca R Das Gupta AU - Annika Saebisch AU - Thomas Grampp AU - Dietmar Benke AU - Hanns Ulrich Zeilhofer AU - Hendrik Wildner TI - Expression of immunoglobulin constant domain genes in neurons of the mouse central nervous system AID - 10.26508/lsa.202101154 DP - 2021 Nov 01 TA - Life Science Alliance PG - e202101154 VI - 4 IP - 11 4099 - https://www.life-science-alliance.org/content/4/11/e202101154.short 4100 - https://www.life-science-alliance.org/content/4/11/e202101154.full SO - Life Sci. Alliance2021 Nov 01; 4 AB - General consensus states that immunoglobulins are exclusively expressed by B lymphocytes to form the first line of defense against common pathogens. Here, we provide compelling evidence for the expression of two heavy chain immunoglobulin genes in subpopulations of neurons in the mouse brain and spinal cord. RNA isolated from excitatory and inhibitory neurons through ribosome affinity purification revealed Ighg3 and Ighm transcripts encoding for the constant (Fc), but not the variable regions of IgG3 and IgM. Because, in the absence of the variable immunoglobulin regions, these transcripts lack the canonical transcription initiation site used in lymphocytes, we screened for alternative 5′ transcription start sites and identified a novel 5′ exon adjacent to a proposed promoter element. Immunohistochemical, Western blot, and in silico analyses strongly support that these neuronal transcripts are translated into proteins containing four Immunoglobulin domains. Our data thus demonstrate the expression of two Fc-encoding genes Ighg3 and Ighm in spinal and supraspinal neurons of the murine CNS and suggest a hitherto unknown function of the encoded proteins.