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F Jirik

Publications and source records attributed to F Jirik.

23 records · Page 2Linked to original sources
PubMed1988

B cell stimulating factor 2/interleukin 6 is a costimulant for human thymocytes and T lymphocytes.

Growth and differentiation of thymocytes and mature T lymphocytes is regulated by cellular interactions that are in part mediated by soluble factors. We identify IL-6, formerly called B cell stimulating factor (BSF-2). IFN-beta 2, or hybridoma-plasmacytoma growth factor (HPGF) as a novel T cell costimulant rIL-6 induced a six-to seven-fold increase in proliferation of human thymocytes stimulated with suboptimal doses of PHA. A similar effect with added IL-6 could be observed using peripheral blood T lymphocytes, but only if the cultures were first rigorously depleted of monocytes that release high levels of IL-6. Analysis of the mechanism of the IL-6 effect on thymocytes and T lymphocytes showed that IL-6 did not lead to an increase in IL-2-R expression. Concentrations of antibody to IL-2-R inhibiting IL-2 effects did not block the IL-6-induced proliferation, indicating that the IL-6 effect was relatively IL-2 independent. These results identify IL-6 as a novel costimulant of human thymocytes and mature T lymphocytes, and suggest that IL-6 is also an important regulatory of cellular immunity.

Cell Division↗
PubMed1987

Molecular basis for the cross-reactive idiotypes on human anti-IgG autoantibodies (rheumatoid factors).

High titres of anti-IgG autoantibodies (rheumatoid factors, RF) are characteristic of patients with rheumatoid arthritis, Sjögren's syndrome, and mixed cryoglobulinaemia, and may contribute to immune complex formation and tissue damage. The monoclonal RFs from cryoglobulinaemia patients frequently display cross-reactive idiotypes. The genetic basis for the cross-reactive idiotypes on RF autoantibodies has not been determined. To clarify structural and genetic relationships among RFs from unrelated subjects, a series of anti-peptide antibodies have been generated that define primary sequence-dependent idiotypes on RF heavy and light chains. Multiple monoclonal and polyclonal RFs from unrelated individuals have been probed by Western blotting with the anti-idiotypic reagents. The results show that sequences in the kappa light chain variable region represent a common structural element among RF autoantibodies. This hypothesis is confirmed by the cloning and sequencing of the conserved germline variable region gene which encodes human RF kappa chains.

Antibody Specificity↗
PubMed1987

Rheumatoid factor and immune networks.

Rheumatoid factors represent a normal component of the immune network. The autoantibodies promote complement fixation and clearance of immune complexes. They amplify the avidity of polyclonally induced IgG. Genes related to the primary structure of rheumatoid-factor light chains are widely distributed in the human population and have been conserved during the evolution and dispersion of the species. Products of these genes may be detected with anti-idiotypic antibodies against synthetic peptides corresponding to individual hypervariable regions on rheumatoid-factor light chains. Such anti-peptide antibodies provide unique reagents for analyzing the genetics of immunoglobulins in outbred populations. Precursors of rheumatoid factor are abundant among immature B lymphocytes. Some of these cells may tend to localize to mucosal surfaces, where they are stimulated directly by pathogenic microorganisms with polyclonal B cell-activating properties. Synthesis of rheumatoid factor regularly accompanies all secondary immune responses but is usually transient. Production of the autoantibody is T-cell dependent. The T cells may recognize antigen in an IgG-antigen immune complex that is processed and presented by B-cell precursors of rheumatoid factor. Rheumatoid factor-associated light-chain idiotypes are rare in serum IgG and on IgG myeloma proteins. They are common among monoclonal IgM proteins and on the surface of the malignant B cells from patients with chronic lymphatic leukemia. The rheumatoid factors that are produced by patients with mixed cryoglobulinemia, or primary Sjogren's syndrome can share idiotypic antigens with monoclonal rheumatoid factors. Rheumatoid factor synthesis in the diseases may reflect an abnormal proliferation of B-cells that is not antigen-driven and that can degenerate into malignancy. The rheumatoid factors in patients with rheumatoid arthritis are diverse and almost certainly represent the outcome of antigen-induced, T cell-dependent mechanisms. The antigens that drive the T cells have not been identified but could represent exogenous microorganisms, self components, or idiotypic antigens that fortuitously interact with rheumatoid factors.

Autoantibodies↗
PubMed1985

The majority of human monoclonal IgM rheumatoid factors express a "primary structure-dependent" cross-reactive idiotype.

Genetic studies of human immunoglobulin variable regions have been hampered by the lack of anti-idiotypic antibodies that recognize specific heavy and light chain variable region sequences. Sixty percent of human monoclonal IgM anti-IgG autoantibodies (rheumatoid factors [RF]) from unrelated individuals share a cross-reactive idiotype (CRI) termed Wa. In previous experiments in which we used an enzyme-linked immunosorbent assay, we reported that a synthetic peptide (PSL2), corresponding to the second hypervariable region in the kappa light chain of a monoclonal IgM-RF (Sie), induced rabbit antibodies reactive with several RF paraproteins. In the present experiments, to avoid interference due to the human IgM-RF binding toward rabbit IgG, the reactivity of the anti-PSL2 antibody to the separated heavy and light chains of multiple IgM proteins and Bence-Jones proteins was assessed by the Western blot technique. The PSL2-induced anti-CRI reacted well with the separated kappa chains from 10 out of 12 IgM-RF, zero out of four light chains from IgM proteins lacking anti-IgG activity, and one out of six kappa Bence-Jones proteins. The results show that the PSL2-CRI is associated with RF and is not a kappa subgroup marker. Furthermore, a comparison of the reported light chain sequences of the PSL2-CRI-positive IgM-RF suggests that the majority of human IgM-RF light chains derive from a single germ-line VK gene or from a family of closely related VK genes that is highly conserved in the human population. Synthetic peptide-induced anti-CRI provide a potent tool for analyzing the genetic basis of CRI and abnormal autoantibody production in humans.

Amino Acid Sequence↗