Receptor Revision of Immunoglobulin Heavy Chain Variable Region Genes in Normal Human B Lymphocytes

doi:10.1084/jem.191.11.1881

Published online 5 June 2000.

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© The Rockefeller University Press, 0022-1007/2000/6/1881/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 11, June 5, 2000 1881-1894

Original Article

Receptor Revision of Immunoglobulin Heavy Chain Variable Region Genes in Normal Human B Lymphocytes

Patrick C. Wilson^a^,b, Kenneth Wilson^a, Yong-Jun Liu^c, Jacques Banchereau^d, Virginia Pascual^d, and J. Donald Capra^a

^a Molecular Immunogenetics Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104
^b Immunology Graduate Program, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235
^c DNAX Research Institute, Palo Alto, California 94304-1104
^d Baylor Institute for Immunological Research, Dallas, Texas 75204
Oklahoma Medical Research Foundation, 825 Northeast 13th St., Oklahoma City, OK 73104.405-271-8237405-271-7210

jdonald-capra{at}omrf.ouhsc.edu

Contrary to the general precepts of the clonal selection theory,several recent studies have provided evidence for the secondaryrearrangement of immunoglobulin (Ig) genes in peripheral lymphoidtissues. These analyses typically used transgenic mouse modelsand have only detected secondary recombination of Ig light chaingenes. Although Ig heavy chain variable region (V_H) genes encodea substantial element of antibody combining site specificity,there is scant evidence for V_H gene rearrangement in the periphery,leaving the physiological importance of peripheral recombinationquestionable. The extensive somatic mutations and clonalityof the IgD⁺Strictly-IgM^–CD38⁺ human tonsillar B cell subpopulationhave now allowed detection of the first clear examples of receptorrevision of human V_H genes. The revised VDJ genes contain "hybrid"V_H gene segments consisting of portions from two separate germlineV_H genes, a phenomenon previously only detected due to the pressuresof a transgenic system.

Key Words: receptor revision • immunoglobulin heavy chain • variable region • recombination • receptor editing

Abbreviations used in this paper: CP, clonal pool; GC, germinalcenter; GFP, green fluorescent protein; RAG, recombination activatinggene; RSS, recombination signal sequence(s); UTR, untranslatedregion.

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