Expression of the immunoglobulin V-H gene 51p1 is proportional to its germline gene copy number

被引:64
作者
Sasso, EH
Johnson, T
Kipps, TJ
机构
[1] UNIV WASHINGTON,DIV RHEUMATOL,SEATTLE,WA 98105
[2] UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093
关键词
B lymphocytes; gene dosage; gene expression; genes; immunoglobulin V-H germline; RFLP;
D O I
10.1172/JCI118644
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
51p1 is an immunoglobulin V-H gene that is frequently expressed in B cell chronic lymphocytic leukemia and early in B cell ontogeny. The 51p1 gene locus is highly polymorphic, consisting of 13 alleles that can be classified as being either 51p1-related or hv1263-related, based on distinctive sequence motifs in the second complementarity determining region, Two of the 51p1-related genes usually occur as a linked pair on the same haplotype, resulting from gene duplication. Consequently, a person can have a total of zero to four copies of 51p1-related genes, These genes are detectable in genomic DNA by sequence-specific RFLP analysis using oligonucleotide probes, Ig encoded by nonmutated 51p1-related genes can be detected by G6, a murine antiidiotypic mAb, We have now studied lymphocytes from 35 human tonsils to examine the relation between the number of 51p1-related germline gene copies and the proportion of IgD-bearing tonsillar B cells that react with G6, All subjects who had zero copies of 51p1-related genes lacked any G6-reactive B cells, whereas those with four copies of 51p1-related genes had the highest proportions of G6-positive IgD B cells, up to 11.4%. Subjects with intermediate gene doses had intermediate proportions of G6-reactive B cells, Over the entire data set, the percentage of IgD-bearing B cells that reacted with G6 was proportional to the 51p1-related gene copy number (r = 0.92, P < 0.001), with each copy accounting for 2.3-4.0% of the IgD-bearing B cells, We conclude that 51p1-related genes are expressed by a relatively large percentage of IgD+ tonsillar B cells and this percentage is proportional to the germline copy number of 51p1-related genes.
引用
收藏
页码:2074 / 2080
页数:7
相关论文
共 35 条
[1]   COMPLETE AMINO-ACID-SEQUENCE OF VARIABLE DOMAINS FROM 2 MONOCLONAL HUMAN ANTI-GAMMA-GLOBULINS OF THE WA CROSS-IDIOTYPIC GROUP - SUGGESTION THAT THE J-SEGMENTS ARE INVOLVED IN THE STRUCTURAL CORRELATE OF THE IDIOTYPE [J].
ANDREWS, DW ;
CAPRA, JD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1981, 78 (06) :3799-3803
[2]   CHARACTERIZATION OF 2 IMMUNOGLOBULIN VH GENES THAT ARE HOMOLOGOUS TO HUMAN RHEUMATOID FACTORS [J].
CHEN, PP ;
LIU, MF ;
GLASS, CA ;
SINHA, S ;
KIPPS, TJ ;
CARSON, DA .
ARTHRITIS AND RHEUMATISM, 1989, 32 (01) :72-76
[3]   A MAP OF THE HUMAN-IMMUNOGLOBULIN V-H LOCUS COMPLETED BY ANALYSIS OF THE TELOMERIC REGION OF CHROMOSOME 14Q [J].
COOK, GP ;
TOMLINSON, IM ;
WALTER, G ;
RIETHMAN, H ;
CARTER, NP ;
BULUWELA, L ;
WINTER, G ;
RABBITTS, TH .
NATURE GENETICS, 1994, 7 (02) :162-168
[4]   THE HUMAN-IMMUNOGLOBULIN V-H REPERTOIRE [J].
COOK, GP ;
TOMLINSON, IM .
IMMUNOLOGY TODAY, 1995, 16 (05) :237-242
[5]  
CROWLEY JJ, 1988, J IMMUNOL, V140, P3411
[6]  
DEANE M, 1991, LEUKEMIA, V5, P646
[7]  
HILLSON JL, 1992, J IMMUNOL, V149, P3741
[8]  
KABAT EA, SEQUENCES PROTEINS I
[9]   UNIFORM HIGH-FREQUENCY EXPRESSION OF AUTOANTIBODY-ASSOCIATED CROSSREACTIVE IDIOTYPES IN THE PRIMARY B-CELL FOLLICLES OF HUMAN-FETAL SPLEEN [J].
KIPPS, TJ ;
ROBBINS, BA ;
CARSON, DA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1990, 171 (01) :189-196
[10]   RELATIONSHIP OF THE CD5 B-CELL TO HUMAN TONSILLAR LYMPHOCYTES THAT EXPRESS AUTOANTIBODY-ASSOCIATED CROSS-REACTIVE IDIOTYPES [J].
KIPPS, TJ ;
DUFFY, SF .
JOURNAL OF CLINICAL INVESTIGATION, 1991, 87 (06) :2087-2096