Abstract
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.
Highlights
Igs are heterodimeric proteins consisting of two heavy and two light chains
We made the surprising observation that Ighg3, the gene that encodes the constant domain of the IgG3 immunoglobulin isotype, was expressed in inhibitory neurons of the mouse spinal cord
We first confirmed this finding with in situ hybridization (ISH) experiments (Fig 1), which revealed an expression pattern highly confined to a thin layer at the border between the superficial and the deep spinal dorsal horn (Fig 1B)
Summary
Igs are heterodimeric proteins consisting of two heavy and two light chains They are produced by B lymphocytes and exert a critical function in the adaptive immune response by binding to pathogens such as bacteria and viruses aiding their neutralization. The variable domain of the heavy chain is encoded by VH, DH, and JH gene segments It is generated through a series of complex gene rearrangements between different VH, DH, and JH segments and is specific for an individual B lymphocyte. B lymphocytes express first monomeric IgM and IgD isotypes using the constant genes Ighm or Ighd, respectively. These naıve B lymphocytes are released from the bone marrow into the blood to populate the periphery via the blood and the lymphatic system (Randolph et al, 2017)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
