title: A mouse with a monoclonal primary immunoglobulin repertoire not further diversified by V-gene replacement.
abstract: We have generated a monoclonal B-cell mouse by introducing homozygous, nonfunctional RAG-2 alleles and a lambda1 light-chain transgene into the quasi-monoclonal (QM) mouse, which contains a "knocked-in" V(H)DJ(H) 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 lambda 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.
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco 94143, USA.
authors.forename: M
authors.initials: M
authors.lastname: Cascalho
authors.forename: D A
authors.initials: DA
authors.lastname: Martin
authors.forename: J
authors.initials: J
authors.lastname: Wong
authors.forename: Q
authors.initials: Q
authors.lastname: Lam
authors.forename: M
authors.initials: M
authors.lastname: Wabl
authors.forename: G E
authors.initials: GE
authors.lastname: Wu
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015322:Gene Rearrangement, B-Lymphocyte; D014644:Genetic Variation; D007132:Immunoglobulin Isotypes / Q000235:genetics* / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic
chemical_list: D007132:Immunoglobulin Isotypes; D007135:Immunoglobulin Variable Region