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Developmental Immunology
Volume 7, Issue 1, Pages 43-50

A Mouse with a Monoclonal Primary lmmunoglobulin Repertoire not Further Diversified by V-Gene Replacement

1Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA
2Department of Immunology, Ontario Cancer Institute, University of Toronto, Toronto, Ontario M5G 2M9, Canada
3Ontario Cancer Institute, Room 8-113, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada

Revised 1 December 1998; Accepted 9 December 1998

Copyright © 1999 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


We have generated a monoclonal B-cell mouse by introducing homozygous, nonfunctional RAG-2 alleles and a λ1 light-chain transgene into the quasi-monoclonal (QM) mouse, which contains a “knocked-in” VHDJH rearrangement. Thus, this mouse, which we call MonoB, is devoid of T cells and contains preformed heavy- and light-chain genes encoding immunoglobulin with an anti-NP specificity. The MonoB mouse allows us to examine immunoglobulin diversity in the absence of processes mediated by V(D)J recombination and T cells. Here we report that not only is the MonoB's primary immunoglobulin repertoire monoclonal, but also that its secondary repertoire is not further diversified by V-gene replacement or gene conversion. Among 99 heavy-chain and 41 λ light-chain genes from peripheral B cells of the MonoB mouse, there were no V-gene replacements. When compared to the QM mouse, which has RAG activity, and for which V-gene replacement is the major diversifying mechanism, these data suggest that V-gene replacement is mediated by V(D)J recombination and not by other recombination systems.