EVIDENCE OF ANTIGEN RECEPTOR-INFLUENCED OLIGOCLONAL B-LYMPHOCYTE EXPANSION IN THE SYNOVIUM OF A PATIENT WITH LONGSTANDING RHEUMATOID-ARTHRITIS

被引:42
作者
LEE, SK
BRIDGES, SL
KIRKHAM, PM
KOOPMAN, WJ
SCHROEDER, HW
机构
[1] UNIV ALABAMA,WALLACE TUMOR INST 362,DEPT MED,DIV DEV & CLIN IMMUNOL,BIRMINGHAM,AL 35294
[2] UNIV ALABAMA,DEPT MICROBIOL,DIV CLIN IMMUNOL & RHEUMATOL,BIRMINGHAM,AL 35294
[3] UNIV ALABAMA,CTR COMPREHENS CANC,BIRMINGHAM,AL 35294
[4] VET ADM MED CTR,BIRMINGHAM,AL 35294
关键词
RHEUMATOID ARTHRITIS; IMMUNOGLOBULINS KAPPA CHAIN; GENES IMMUNOGLOBULIN; ANTIBODY DIVERSITY; B LYMPHOCYTES;
D O I
10.1172/JCI116968
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
Plasma cell infiltration of synovium is common in longstanding rheumatoid arthritis( RA). The mechanism(s) underlying synovial B cell proliferation remains unclear. One theory invokes nonspecific polyclonal stimuli; another implicates antigen as the driving force. Antigen-driven repertoires are characteristically enriched for related sets of V gene segments containing similar sequence in the antigen binding site (complementarity-determining regions; CDRs). To study the forces shaping B cell proliferation, we analyzed V kappa transcripts expressed in the synovium of an RA patient. We found Humkv325, a developmentally regulated V kappa III gene segment associated with autoantibody reactivity, in > 10% of randomly-chosen synovial C kappa cDNAs. Two sets of sequences contained identical charged amino acid residues at the V kappa-J kappa join, apparently due to N region addition. We generated ''signature'' oligonucleotides from these CDR3s and probed PCR amplified V kappa products from the synovium and PBLs of the same patient, and from PBLs and spleen of individuals without rheumatic disease. Significant expression of transcripts containing these unique CDR3 sequences occurred only in the patient's synovium. Thus, in this synovium there is expansion of a limited set of B cell clones expressing antigen receptors that bear evidence of antigen selection.
引用
收藏
页码:361 / 370
页数:10
相关论文
共 52 条
  • [1] ABOLA EE, 1987, CRYSTALLOGRAPHIC DAT, P107
  • [2] JOINING OF IMMUNOGLOBULIN HEAVY-CHAIN GENE SEGMENTS - IMPLICATIONS FROM A CHROMOSOME WITH EVIDENCE OF 3 D-JH FUSIONS
    ALT, FW
    BALTIMORE, D
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1982, 79 (13): : 4118 - 4122
  • [3] PREDOMINANCE OF T CELLS IN LYMPHOCYTIC INFILTRATES OF SYNOVIAL TISSUES IN RHEUMATOID-ARTHRITIS
    BANKHURST, AD
    HUSBY, G
    WILLIAMS, RC
    [J]. ARTHRITIS AND RHEUMATISM, 1976, 19 (03): : 555 - 562
  • [4] PROTEIN DATA BANK - COMPUTER-BASED ARCHIVAL FILE FOR MACROMOLECULAR STRUCTURES
    BERNSTEIN, FC
    KOETZLE, TF
    WILLIAMS, GJB
    MEYER, EF
    BRICE, MD
    RODGERS, JR
    KENNARD, O
    SHIMANOUCHI, T
    TASUMI, M
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1977, 112 (03) : 535 - 542
  • [5] GENETIC-BASIS FOR THE CROSS-REACTIVE IDIOTYPES ON THE LIGHT-CHAINS OF HUMAN-IGM ANTI-IGG AUTOANTIBODIES
    CHEN, PP
    ALBRANDT, K
    ORIDA, NK
    RADOUX, V
    CHEN, EY
    SCHRANTZ, R
    LIU, FT
    CARSON, DA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (21) : 8318 - 8322
  • [6] ISOLATION OF BIOLOGICALLY-ACTIVE RIBONUCLEIC-ACID FROM SOURCES ENRICHED IN RIBONUCLEASE
    CHIRGWIN, JM
    PRZYBYLA, AE
    MACDONALD, RJ
    RUTTER, WJ
    [J]. BIOCHEMISTRY, 1979, 18 (24) : 5294 - 5299
  • [7] DERSIMONIAN H, 1989, J IMMUNOL, V142, P4027
  • [8] INSERTION OF N REGIONS INTO HEAVY-CHAIN GENES IS CORRELATED WITH EXPRESSION OF TERMINAL DEOXYTRANSFERASE IN B-CELLS
    DESIDERIO, SV
    YANCOPOULOS, GD
    PASKIND, M
    THOMAS, E
    BOSS, MA
    LANDAU, N
    ALT, FW
    BALTIMORE, D
    [J]. NATURE, 1984, 311 (5988) : 752 - 755
  • [9] SINGLE-STEP SEPARATION OF RED BLOOD-CELLS, GRANULOCYTES AND MONONUCLEAR LEUKOCYTES ON DISCONTINUOUS DENSITY GRADIENTS OF FICOLL-HYPAQUE
    ENGLISH, D
    ANDERSEN, BR
    [J]. JOURNAL OF IMMUNOLOGICAL METHODS, 1974, 5 (03) : 249 - 252
  • [10] IMMUNOGLOBULIN-KAPPA LIGHT CHAIN GENE PROMOTER AND ENHANCER ARE NOT RESPONSIBLE FOR B-CELL RESTRICTED GENE REARRANGEMENT
    GOODHARDT, M
    BABINET, C
    LUTFALLA, G
    KALLENBACH, S
    CAVELIER, P
    ROUGEON, F
    [J]. NUCLEIC ACIDS RESEARCH, 1989, 17 (18) : 7403 - 7415