Somatic translocation and differential expression of Ig mu transgene copies implicate a role for the Igh locus in memory B cell development.
Memory B cells of mice with Ig mu transgenes often carry transgene copies that have moved into the Igh locus via somatic translocation. This phenomenon has been attributed to a selection pressure for somatic hypermutations, which generally are observed at much higher frequencies in translocated copies than in ectopic copies. We tested this idea by immunizing Ig-mu transgenic mice in a manner designed to select B cells that required only one V(H) mutation for a switch in antigenic specificity and recruitment into the memory pool. Despite the minimal mutation requirement, hybridomas carrying somatic translocations to the Igh locus were obtained. Importantly, this occurred despite the fact that translocated and untranslocated mu-transgenes were mutated comparably. Evidently, a strong selection advantage was conferred upon B cells by the somatic translocations. Among the hybridomas, translocated mu-transgenes were active, while ectopic mu-transgenes were uniformly silent. The translocated copy that had conferred an affinity-based selection advantage was expressed at the highest level. Moreover, translocated copies were differentially expressed among hybridoma members, which belonged to a common post-mutational lineage. This suggests that adjustments in transgene expression levels had occurred during memory cell development. These results indicate that, apart from their potential influences on somatic hypermutagenesis and class switch recombination, elements in the Igh locus promote the selection of memory B cells in another way, possibly by regulating the level of Ig expression at various stages of antigen-driven differentiation.
Jena
Prasanna K
PK
Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver, CO 80206, USA.
Smith
Diana S
DS
Zhang
Xianghua
X
Aviszus
Katja
K
Durdik
Jeannine M
JM
Wysocki
Lawrence J
LJ
D000818:Animals; D001147:Arsanilic Acid / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001483:Base Sequence; D002454:Cell Differentiation; D019070:Cell Lineage; D005786:Gene Expression Regulation / Q000276:immunology*; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D006433:Hemocyanins / Q000276:immunology; D006825:Hybridomas / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007148:Immunoglobulin mu-Chains / Q000235:genetics*; D007156:Immunologic Memory / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics / Q000276:immunology; D019076:Transgenes
D007135:Immunoglobulin Variable Region; D007148:Immunoglobulin mu-Chains; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D001147:Arsanilic Acid