The kinetics of immunoglobulin-synthesizing cells (IFC) and antibody-forming cells (AFC) are compared in the popliteal nodes of mice challenged, in the hind footpads, with horseradish peroxidase (PO) in Freund's complete adjuvant. A rise in the number of IFC without antibody function precedes the appearance of AFC. IFC reach peak numbers 7 days before AFC. Control experiments show that the majority of IFC without antibody function are responding to PO and not to adjuvant. Kinetic and radioautographic data suggest that IFC arise by division and differentiation; however, the doubling time of AFC is too rapid to be accounted for by cell division alone. Double staining techniques revealed the presence of immunoglobulin and antibody in different compartments of the same cell in 5 to 15% of the AFC. It is postulated that some AFC are recruited, possibly from cells already synthesizing immunoglobulin determinants.
A bstract : Interleukin‐1 receptors (lL‐1R type I and II) have been characterized in murine nervous structures (hippocampus and frontal cortex), in vascular structures (vessels, choroid plexus), and in the anterior pituitary. Because interleukin‐1 (IL‐ 1), injected or induced in the brain, is a powerful regulator of the stress axis and immune functions, it was of interest to investigate IL‐1Rs and IL‐1 in autoimmune mice. In control mice, bacterial lipopolysaccharide (LPS), administered i.p. or i.c.v., induces a sharp decrease in available brain IL‐1 receptors, in spite of a moderate increase in mRNAs for both receptor types. This is concomitant with an increase in IL‐1α, β, and ra mRNA. Ligand production clearly overcomes receptor turnover. In autoimmune mice (NZB and NZB/NZW F1), a strong defect in IL‐1R (type I) is demonstrated in the dentate gyrus. This tissue‐specific defect cannot be explained by increased occupancy by endogeneous ligands as for LPS‐treated mice. The transmission of the defect is Mendelian and suggests the involvement of a single gene. However patterns of IL‐1R mRNAs (evaluated by RT‐PCR) are similar in NZB and in controls, suggesting a translational or post‐translational abnormality. The contribution of this genetic disorder in the development of autoimmunity remains to be clarified. Because the brain IL‐1 system sends inhibitory signals towards immune functions, this lack of functional IL‐1 binding sites might participate in the disregulations observed in NZB autoimmune mice.
In the serum of normal BALB/c mice, IgG antibody reactivity to mouse actin and tubulin, DNA, and TNP groups was very low compared to that of the IgM. This activity was considerably increased when IgG was separated, by affinity chromatography on protein A-Sepharose, whereas no difference in the IgM activity was observed. Addition of IgM to IgG isolated from the same serum resulted in the inhibition of IgG binding to these Ag. Isolation of IgG antibodies on actin, TNP, and tubulin immunoadsorbents has indicated that at least part of the IgG antibodies is polyreactive. In order to understand this inhibition better, experiments with F(ab')2 fragments of IgG were performed. IgM inhibited the binding of F(ab')2 to the antigens in a dose-dependent manner and reacted with immobilized F(ab')2. IgM isolated on F(ab')2 immunoadsorbent, as compared to the initial IgM preparation, were less active toward the Ag but more inhibitory for IgG binding to the Ag. In some pathologic situations, IgM failed to inhibit some IgG antibody activities. The anti-DNA IgG activity from (NZB x NZW)F1 mice was not affected by autologous IgM. Similarly the anti-tubulin IgG from mice infected with Trypanosoma cruzi were less inhibited by IgM from autologous serum than antitubulin IgG from normal mice. These results are compatible with the existence in normal mice of an idiotypic-like network, regulating via an IgM population in the serum, the binding of IgG autoantibodies to self Ag. Modifications of this idiotype-anti-idiotype system might lead to the expression and/or expansion of autoreactive IgG-producing clones.
Mice were injected in their hind footpads with peroxidase (PO) emulsified in Freund's complete adjuvant. The development of cells secreting anti-peroxidase antibody (Ab) and cells secreting immunoglobulins (Ig) were detected in the draining popliteal lymph nodes in the subsequent 35 days, using local haemolysis plaque assay with sheep red cell blood cells coated with either PO or anti-mouse Ig antibody. Plaque-forming cells (PFC) were isolated from the centre of plaques by micromanipulation and after appropriate treatment, were examined by electron microscopy for their intracellular Ab content and in corporation of [3H]-thymidine. Four subpopulations of Ig secreting cells were distinguished: (1) cells secreting Ig without Ab function and not containing intracellular Ab detectable between days 5 and 20; (2) cells secreting Ig without Ab function but containing Ab appearing on day 6 and present throughout the immune response; (3) cells secreting Ab and containing Ab; (4) cells secreting Ab, but without detectable intracellular Ab. These last subpopulations appeared on day 7 and were found in all subsequent assays. The analysis of the kinetics of these subpopulations suggest that cells secreting Ig without Ab function might be precursors of Ab secreting cells.
