The goals of this research project have been to understand something of the germline contribution to the anti-arsonate immune response in A/J mice. Toward the end, we have cloned and sequenced the VH, DH, JH and VK and JK germline gene segments that give rise to this response. In addition, we have cloned and sequenced eleven related VH and three related VK germline gene segments. A considerable amount of attention was paid to the organization of the VH locus in the A/J strain and using deletion mapping, the J558 gene family (to which the Ars-A VH gene segment belongs) was oriented relative to other gene families. In addition, the 3660 VH family (to which the Ars-C VH gene segment belongs) was also oriented within the A/J VH locus. We detected several differences between the orientation of the A/J VH complex and the accepted Balb/c organization. Further studies are planned to explore A/J V gene segment organization and control. Studies directed toward an understanding of transcription initiation focused on nuclear proteins that bind to immunoglobulin VH octamer sequences. The arsonate as well as the BCL1 systems were used in this regard and during the next five years, a considerable effort will be made toward further defining the proteins involved in this interaction as well as cloning the genes that encode them. By this means we hope to understand more of transcriptional regulation of immunoglobulin genes. A constant correlation has been and continues to be made between the germline component of the arsonate idiotypic system and the expressed proteins. Experiments are described in which this relationship is explored from the perspective of N segment diversity, junctional diversity, gene conversion, and somatic mutation.
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