The Journal of Experimental Medicine
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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. Wilsona,b, Kenneth Wilsona, Yong-Jun Liuc, Jacques Banchereaud, Virginia Pascuald, and J. Donald Capraa

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 secondary rearrangement of immunoglobulin (Ig) genes in peripheral lymphoid tissues. These analyses typically used transgenic mouse models and have only detected secondary recombination of Ig light chain genes. Although Ig heavy chain variable region (VH) genes encode a substantial element of antibody combining site specificity, there is scant evidence for VH gene rearrangement in the periphery, leaving the physiological importance of peripheral recombination questionable. The extensive somatic mutations and clonality of the IgD+Strictly-IgM–CD38+ human tonsillar B cell subpopulation have now allowed detection of the first clear examples of receptor revision of human VH genes. The revised VDJ genes contain "hybrid" VH gene segments consisting of portions from two separate germline VH genes, a phenomenon previously only detected due to the pressures of a transgenic system.

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

Abbreviations used in this paper: CP, clonal pool; GC, germinal center; GFP, green fluorescent protein; RAG, recombination activating gene; RSS, recombination signal sequence(s); UTR, untranslated region.

© 2000 The Rockefeller University Press


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