[Mutational pattern of Ig-VH genes of synovial B-lymphocytes from different anatomical locations in a rheumatoid arthritis patient].
Synovial B-lymphocytes which are a constant feature of RA synovialitis are expanded in an antigen dependent manner. To understand the nature of the antigen driving the B-cell expansion it would be interesting to know whether there exists a restricted number of antigens. Therefore the usage of germline genes and the mutational pattern of Ig-VH-genes from synovial B-cells from 3 different anatomical regions with different onsets of local disease were analysed. Together with an immunohistological study characterising the inflammatory infiltrate (CD3, CD22, CD23 and Ki-M4), RNA was prepared from tissue sections taken from the right and left peroneal tendons and right elbow of a patient with seropositive RA. The corresponding cDNA was amplified using specific VH primers and the obtained variable region sequences were compared to their closest germline counterparts on the EMBL/Genbank data base. The molecular analysis demonstrated somatically mutated VH genes (total R/S ratios in CDR 1 + 2: right peroneal tendon 7.5; left peroneal tendon 3.5 and right elbow 3.0) in all three different regions, with two clones presenting aminoacid deletions. The values of total R/S ratios correlated directly to the duration of local disease. The aminoacid sequences from the different locations exhibited strong homology among each other. This homology was of 77% for the 19 clones belonging to the VH1 family. Immunohistochemistry demonstrated in two locations a dense follicle-like infiltrate with FDC-network, the third location presented a non-follicular distribution of lymphozytes without FDC. Hence the R/S values were correlated directly with the duration of local disease, it appears that here is an ongoing antigen-dependent B-cell activation in joints probably occurring in the FDC-networks. Moreover this study suggests--due to a high homology among the VH aminoacid sequences from B-cells of different anatomical regions--that a restricted number of antigens is involved in the B-cell expansion of RA patients.
Souto-Carneiro
M M
MM
Pathologisches Institut der Universität Würzburg.
Krenn
V
V
Hermann
R
R
Ristow
G
G
König
A
A
Müller-Hermelink
H K
HK
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D004551:Elbow Joint; D005260:Female; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013583:Synovial Membrane / Q000276:immunology* / Q000473:pathology; D013710:Tendons
D015703:Antigens, CD; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region