The B lymphocyte in rheumatoid arthritis: analysis of rearranged Vx genes from B cells infiltrating the synovial membrane
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Abstract The participation of the humoral immune system in rheumatoid arthritis (RA) is characterized by the production of rheumatoid factors (RF). RF are autoantibodies against the Fc part of IgG which are encoded by diverse germ‐line genes. Most of the RF‐encoding genes are unmutated, but in RA, a substantial quantity is encoded by somatically mutated genes. In addition, the synovial membranes (SM) of the diseased joints of RA patients are infiltrated by B lymphocytes which form germinal center‐like aggregates. To analyze the local immune response, B cell foci from two RA SM were isolated by micromanipulation. From DNA of these foci, the rearranged kappa light chain variable region (Vx) genes were amplified by polymerase chain reaction (PCR), cloned and sequenced. The amplification of different Vx‐Jx combinations of different foci suggested oligoclonal expansion of B lymphocytes, which was confirmed by sequence analysis: each PCR product contained members of a single B cell clone. The sequence analysis of 29 different clones revealed rearrangements of diverse Vx genes. Both frequent representatives of the Vx3 and the Vx1 family, as well as rarely used genes such as the L10 and B2 genes of the Vx2 and Vx5 families were found. Of the eleven potentially functional gene rearrangements, eight were significantly mutated, indicating their derivation from antigen‐selected B cells. Intraclonal diversity in one of these clones may suggest ongoing mutation in the diseased synovial membrane of patients with RA.Preoperative and postoperative studies of peripheral B and T lymphocyte counts were accomplished in 21 patients. Diagnoses included 10 carcinoma of the breast, 3 sarcoma, and 8 benign diseases. On postoperative day one and two, an increase in B-cell percentage was observed in the majority of patients tested. However, there was a decrease in total lymphocyte count and fast-reacting T lymphocyte numbers on postoperative day one, especially in patients who had intraabdominal operations. All the lymphocyte counts returned to preoperative range within one week. Pertinent reports in the literature were reviewed and discussed.
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Peripheral blood lymphocyte
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Objectives : BALB/c mice were administered with JeEoTmg extract after rheumatoid arthritis elicitation were observed to investigate the mitigative effect of JeEoTang for rheumatoid arthritis. Methods : The JeEoTang extract(3.3 ml/kg/day) was daily administered for 14 days to mice suffered from rheumatoid arthritis induced by LPS(300 pt/kg). These specimens were decalcificated in EDTA solution for 4 Weeks. Results : All parameters involved in the rheumatoid arthritis of synovial membrane - hyperplasia of synoviocytes, fibrosis, angiogensis. and infiltration of inflammatory cells - were dramatically decreased in JeEoTmg extract administered mice. The number of NK-1.1, IL-lP, IL-2R-a, and ICAM-1 positive cells in synovial membrane was also remarkably diminished in JeEoTmg extract administered mice and apoptotic cell was decreased. Conclusions : These results indicate that the immnue suppression of JeEoTmg work on the mitigation of synovial damages in mice with rheumatoid arthritis, subsequently JeEoTung may play a role as a cure for rheumatoid arthritis.
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Abstract Lymphocytes from patients with rheumatoid arthritis were studied in one‐way stimulation mixed leukocyte culture (MLC) and results compared with cultured pairs of rheumatoid and normal lymphocytes. In 14 of 22 experiments, no lymphocyte stimulation was noted when rheumatoid arthritis lymphocytes obtained from unrelated patients were studied in MLC. Normal lymphocytes produced stimulation of rheumatoid cells in 16 of 22 instances, and rheumatoid lymphocytes induced transformation of normal subjects' lymphocytes in 19 of 22 experiments. Marked alteration in mutual lymphocyte stimulation was thus recorded when cells from some patients with rheumatoid arthritis were studied together.
Mixed lymphocyte reaction
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Objective: The purpose of our study is to investigate the effect of phototherapy on lymphocyte subsets in the treatment of hyperbilirubinemia in neonates. Material and Methods: Twenty two term infants as the study group and 25 term infants as the control group were hospitalized. Lymphocyte subsets levels were investigated in blood samples during hospitalization in all infants. However, subsets levels were investigated before and eight hours after the phototherapy, and once again after 48 hours in 16 infants in the study group. Results: The lymphocyte count of infants in the study and control groups were found similar, as well as the lymphocyte subsets ratios. Apart from CD4+ lymphocyte count of the study group eight hours after the phototherapy, any significant change was not observed in lymphocyte subsets. However, significant increase was determined in CD4+ ratios after phototherapy (p< 0.05). Any significant change was not determined in lymphocyte count and lymphocyte subsets 48 hours after phototherapy (p> 0.05). Conclusion: Apart from CD4+ count eight hours after phototherapy, any effect was not determined on the whole T-lymphocyte profile after 48 hours. Therefore, we assume that the possible effects of phototherapy on the immune system is not directly related to the effects on T-lymphocytes. The increase in CD4+ which appears eight hours after phototherapy requires more detailed studies regarding the effect of phototherapy on the immune system.
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Abstract The effect of synovial fluid and washings of synovial membrane on autologous lymphocytes from patients with rheumatoid arthritis and other diseases has been studied using a rapid method based upon the increase in intranuclear birefringence occurring in the early stages of lymphocyte activation. Retardation of polarized light indicating increased lymphocyte activation was seen in lymphocytes from patients with rheumatoid arthritis but not in lymphocytes from patients with other diseases.
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Medical microbiology
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Peripheral blood leukocytes (PBL) from patients with rheumatoid arthritis (RA) and from control subjects were exposed to rheumatoid and osteoarthritic synovial membrane extracts. The number of nonadherent PBL in the presence of each extract was monitored in a test tube leukocyte adherence inhibition (LAI) assay. Six of 7 rheumatoid synovial extracts produced significantly greater nonadherence values when RA leukocytes were used as the test cell (36 +/- 5) compared with values obtained when control leukocytes were used (-5 +/- 3). Preincubation of LAI reactive leukocytes from RA patients with the RA synovial extracts abrogated the positive response, whereas preincubation with the OA extract had no effect. These studies indicate that leukocytes from RA subjects respond to a greater degree to extracts derived from rheumatoid synovium than to extracts derived from osteoarthritic synovium and add further support to the concept that unique substances (putative neoantigens?) are present in RA synovium.
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Objectives : BALB/c mice were administered with JeEoTmg extract after rheumatoid arthritis elicitation were observed to investigate the mitigative effect of JeEoTang for rheumatoid arthritis. Methods : The JeEoTang extract(3.3 ml/kg/day) was daily administered for 14 days to mice suffered from rheumatoid arthritis induced by LPS(300 pt/kg). These specimens were decalcificated in EDTA solution for 4 Weeks. Results : All parameters involved in the rheumatoid arthritis of synovial membrane - hyperplasia of synoviocytes, fibrosis, angiogensis. and infiltration of inflammatory cells - were dramatically decreased in JeEoTmg extract administered mice. The number of NK-1.1, IL-lP, IL-2R-a, and ICAM-1 positive cells in synovial membrane was also remarkably diminished in JeEoTmg extract administered mice and apoptotic cell was decreased. Conclusions : These results indicate that the immnue suppression of JeEoTmg work on the mitigation of synovial damages in mice with rheumatoid arthritis, subsequently JeEoTung may play a role as a cure for rheumatoid arthritis.
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Objectives : BALB/c mice were administered with JeEoTmg extract after rheumatoid arthritis elicitation were observed to investigate the mitigative effect of JeEoTang for rheumatoid arthritis. Methods : The JeEoTang extract(3.3 ml/kg/day) was daily administered for 14 days to mice suffered from rheumatoid arthritis induced by LPS(300 pt/kg). These specimens were decalcificated in EDTA solution for 4 Weeks. Results : All parameters involved in the rheumatoid arthritis of synovial membrane - hyperplasia of synoviocytes, fibrosis, angiogensis. and infiltration of inflammatory cells - were dramatically decreased in JeEoTmg extract administered mice. The number of NK-1.1, IL-lP, IL-2R-a, and ICAM-1 positive cells in synovial membrane was also remarkably diminished in JeEoTmg extract administered mice and apoptotic cell was decreased. Conclusions : These results indicate that the immnue suppression of JeEoTmg work on the mitigation of synovial damages in mice with rheumatoid arthritis, subsequently JeEoTung may play a role as a cure for rheumatoid arthritis.
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