DUCK ANTIBODY GENES--UNUSUAL ORGANIZATION AND EXPRESSION

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The duck's immune system functions poorly, and has been described as inept. This species is susceptible to infectious disease, which has an impact on human health through the farming of ducks and because of the important role of ducks in the ecology of the influenza A virus. The long-term objective of these proposed studies is to understand the immunogenetic basis of the duck's antibody response. Initial studies have shown that 2 of the genes encoding antibody heavy chain constant (C) regions in the duck (the alpha and upsilon genes) are in head-to-head orientation. The specific aims of the proposed work seek to answer the following questions. 1) Is the order of C region genes in the duck IgH locus (mu-alpha-upsilon) or (mu-upsilon- alpha)? Did the recombination events that produced the reorganization of the duck IgH locus result in the loss of the membrane exon associated with the alpha gene? 3) Is there a homolog of the delta gene present in the duck IgH locus? 4) In what manner does the head-to-head orientation of the upsilon and alpha genes affect the process of class switching to IgY or IgA in duck B cells? These questions will be approached through cloning and mapping of the duck IgH locus (by use of recombinant genomic phage and bacterial artificial chromosome libraries) and sequencing of critical regions of the locus. The nature of class-switching mechanisms will be investigated by the isolation and analysis of the circular DNA products of class switch recombination. The results of these proposed studies should provide insight into the manner in which specific aspects of C gene organization, such as head-to-head orientation, affect the functional expression of these genes, and add to our knowledge of the functional significance of different gene organizations found in the vertebrate IgH locus.