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Limits on heavy chain junctional diversity contribute to the recurrence of an antibody variable region

Molecular Immunology
Publication Date
DOI: 10.1016/0161-5890(90)90069-c
  • Mathematics


Abstract Antibody V region structural diversity in the mouse is generated, in part, by the combinatorial joining of different gene segments, as well as by the “imprecision” of these joining events. The same two gene segments can be joined at different locations, and nucleotides can be deleted or added de novo to the segment junction. While it is clear that such junctional processes are a major contributor to V region diversity, the mechanisms that generate this diversity are poorly understood. Here I present sequences in the v H-D-j H region of 34 V H genes that are composed of the same three V H gene segments. In combination with a single V K-J K pair, these V H genes encode a family of V regions that are recurrently expressed in the immune response of A/J mice to p-azophenylarsonate (Ars). The germline sequences of the three constituent gene segments for these V H genes are known, making it possible to determine the origin of the nucleotides in junctional regions. An examination of the frequency and type of nucleotides present in these regions provides insight into the properties of the segment joining mechanism. In addition, the data suggest that recurrent expression of the anti-Ars V regions which these V H genes partially encode is due not only to antigenic selection, but to the high probability with which these V H genes are formed during B cell differentiation.

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