cDNA libraries for IgM heavy chain variable regions were prepared from unmanipulated peripheral blood lymphocytes of two healthy people. Partial sequencing of 103 clones revealed VH gene family use and complete CDR3 and JH sequences. The libraries differed in the two subjects. In one person's cDNA the VH5 family was overexpressed and the VH3 family underexpressed relative to genomic complexity. In the second person's cDNA, VH3 was most frequently expressed. In both libraries, JH4 was most frequent. VH segments of several clones were closely related to those in fetal repertoires. However, there was also evidence of mutation in many cDNAs. Three clones differed from the single nonpolymorphic VH6 germline gene by 7-13 bases. Clones with several differences from VH5 germline gene VH251 were identified. CDR3 segments were highly diverse. JH portions of several CDR3's differed from germline JH sequences. 44% of the clones had DH genes related to the DLR and DXP families, most with differences from germline sequences. In 11 DLR2-related sequences, several base substitutions could not be accounted for by polymorphism. Thus, circulating IgM-producing B cell populations include selected clones, some of which are encoded by variable region gene segments that have mutated from the germline form.
C Huang, A K Stewart, R S Schwartz, B D Stollar
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Variable region gene analysis of B cell subsets derived from a 4-year-old child: somatically mutated memory B cells accumulate in the peripheral blood already at young age
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The human immunoglobulin VH7 gene family consists of a small, polymorphic group of six to eight gene segments dispersed throughout the VH locus
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High-frequency representation of a single VH gene in the expressed human B cell repertoire
AK Stewart, C Huang, BD Stollar, RS Schwartz |
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Human immunoglobulin heavy-chain minilocus recombination in transgenic mice: gene-segment use in mu and gamma transcripts
N Tuaillon, LD Taylor, N Lonberg, PW Tucker, JD Capra |
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Light and heavy chains specifying a human IgMκ autoantibody to a T-cell receptor Vβ-antigen
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Human IgM+IgD+ B cells, the major B cell subset in the peripheral blood, express Vϰ genes with no or little somatic mutation throughout life
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Structure of the VH and VL segments of polyreactive and monoreactive human natural antibodies to HIV-1 and Escherichia coli beta-galactosidase
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International Immunology | 1993 |
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Journal of immunology (Baltimore, Md. : 1950) | 1993 |
VH-Gene Representation in Autoantibodies Reflects the Normal Human B-Cell Repertoire
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Immunological Reviews | 1992 |
High frequency of somatically mutated IgM molecules in the human adult blood B cell repertoire
JH van Es, FH Meyling, T Logtenberg |
European Journal of Immunology | 1992 |
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EH Sasso |
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