A biological consequence of variation in the site of d–jh gene rearrangement

ABSTRACT One mechanism which generates diversity in immunoglobulin variable (V) regions is flexibility in the site of recombination among the constituent genetic elements1–7. Within a

specific antibody family (that is, a particular VH–VL combination), variability in _V–D–J_ rearrangement not only leads to sequence diversity at the boundary of the juxtaposed genes, but

also enables the total length of the third complementarity-determining region (CDR-3) of the heavy chain to be conserved8. We demonstrate here that the junctional diversity inherent in

rearranged immunoglobulin genes can have consequences for the biology of the immune system. Sequence analysis of the expressed immunoglobulin genes of idiotypically variant as opposed to

conventional B lymphocytes of a dominant antibody family showed that the variant B cells undergo a novel D–JH joining event such that an extra amino acid is inserted into the heavy chain

CDR-3. The unique D-region conformation possessed by the variant B cells accounts for previous observations which showed that variant and conventional B cells could be differentially

regulated _in vivo_ by an autologous set of idiotope-specific B lymphocytes9. Our findings indicate that D-region structure can determine the expression of regulatory idiotopes and suggest

that the conservation of heavy-chain CDR-3 length within an antibody family may reflect regulatory as well as functional constraints. Access through your institution Buy or subscribe This is

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INVERTED D GENES AND D-D FUSIONS IN HUMAN ANTIBODY REPERTOIRES UNLOCKS NOVEL ANTIBODY DIVERSITY Article Open access 28 January 2025 NEW INSIGHTS INTO ANTIBODY STRUCTURE WITH IMPLICATIONS FOR

SPECIFICITY, VARIABLE REGION RESTRICTION AND ISOTYPE CHOICE Article 20 March 2025 FUNCTIONAL ANTIBODIES EXHIBIT LIGHT CHAIN COHERENCE Article Open access 26 October 2022 REFERENCES *

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Chase Cancer Center, Philadelphia, Pennyslvania, 19111, USA Brian A. Pollok & Robert P. Perry * Cellular Immunobiology Unit, Department of Microbiology, University of Alabama in

Birmingham, Birmingham, Alabama, 35924, USA John F. Kearney & Meenal Vakil Authors * Brian A. Pollok View author publications You can also search for this author inPubMed Google Scholar

* John F. Kearney View author publications You can also search for this author inPubMed Google Scholar * Meenal Vakil View author publications You can also search for this author inPubMed 

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THIS ARTICLE Pollok, B., Kearney, J., Vakil, M. _et al._ A biological consequence of variation in the site of _D–J_H gene rearrangement. _Nature_ 311, 376–379 (1984).

https://doi.org/10.1038/311376a0 Download citation * Received: 28 February 1984 * Accepted: 18 July 1984 * Issue Date: 27 September 1984 * DOI: https://doi.org/10.1038/311376a0 SHARE THIS

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