Immunoglobulin D (IgD) is an enigmatic antibody isotype that mature B cells co-express with IgM through alternative RNA splicing. We found active T cell-dependent and T cell-independent IgM-to-IgD class switching in human upper respiratory mucosa B cells. This process required activation-induced cytidine deaminase and generated local and circulating IgD-producing plasmablasts reactive to respiratory bacteria. Circulating IgD bound to basophils through a calcium-mobilizing receptor that induced antimicrobial, opsonizing, inflammatory and B cell-stimulating factors including cathelicidin, interleukin-1, interleukin-4 and B cell-activating factor BAFF upon IgD cross-linking. By showing dysregulation of IgD class-switched B cells and IgD-armed basophils in autoinflammatory syndromes with periodic fever, our data indicate that IgD orchestrates an ancestral surveillance system at the interface between immunity and inflammation.
IgD is considered to be a recently evolved Ig, being previously found only in primates and rodents. Here we describe, from a teleost fish (the channel catfish, Ictalurus punctatus), a novel complex chimeric Ig heavy chain, homologous, in part, to the heavy chain (␦) of IgD. In addition to alternative secretory or membrane-associated C termini, this chimeric molecule contains a rearranged variable domain, the first constant domain of , and seven constant domains encoded by a ␦ gene homolog. Identification of the catfish gene as ␦ is based on the following properties: sequence relatedness to mammalian ␦; a location within the IgH locus that is immediately downstream of the gene; separate terminal exons for the secretory and membrane forms; coexpression with the complete chain in some but not all B cells. These results (i) suggest that IgD is an ancient immunoglobulin that was present in vertebrates ancestral to both the mammals and the ray-finned fishes, and (ii) raise the possibility that this Ig isotype may have served an as yet unidentified important function early in the evolution of the immune system.
A monoclonal antibody to trout serum IgM was tested by immunofluorescence analysis with lymphocytes from thymus, spleen and head kidney. By visual examination, the antibody reacted with only a subpopulation of lymphocytes. The mean values +/- SE for positive cells were 5.2 +/- 2.3% in the thymus, 30.3 +/- 7.9% in the spleen and 12.4 +/- 3.0% in the head kidney. Flow cytofluorometric analysis revealed evidence of heterogeneity by size among the membrane IgM-positive cells of the head kidney and spleen. Depletion of head kidney cells positive for surface IgM by an immune affinity adherence technique of panning, using monoclonal anti-IgM, significantly reduced the mitogenic response to lipopolysaccharide but not to concanavalin A. It is suggested that this information supports the existence of distinct subpopulations of fish lymphocytes that may be homologous in certain respects to mammalian T and B type cells.
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