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The effect of human C-reactive protein (CRP) isolated and purified from pooled patients' sera on macrophage function, especially on macrophage migration, was studied. Peritoneal exudate cells (PEC) from guinea pigs were used for macrophage migration inhibition (MMI) test of capillary method. Migration of either PEC or adherent purified macrophages exposed to CRP were inhibited dose-dependently. These findings indicate that CRP inhibits macrophage migration directly, not via activation of lymphocytes contained in PEC. As control, we examined the effect of normal human serum, anti C-polysaccharide antibodies isolated from patients' sera, and free endotoxin at the dose contaminated in CRP preparation on macrophage migration and found that none of them were effective. The effect of CRP on MMI of sensitized PEC exposed to antigen was also studied. Large amounts of CRP inhibited MMI induced by antigen, indicating the possibility that CRP may act on macrophages competitively with migration inhibitory factor (MIF) and may modulate MMI. CRP possesses MIF-like activity and may play a functional role at the site of tissue injury by causing the accumulation of macrophages.

Serum from a patient (KK) with IgG2‐λ myeloma was shown to contain multiple paraproteins corresponding to an IgM‐λ monoclonal protein (MMP), a λ‐type Bence Jones protein (BJP), and a 30 kDa component in addition to the IgG2 myeloma protein (GMP). These proteins possessed common idiotypic determinants, as judged by their monoclonal reactivity with rabbit anti‐GMP idiotype antibody (aId) in the immunofixation electrophoresis. Analysis with aId absorbed with either H or L chain of GMP revealed that the 30 kDa component shared both VH and VL with GMP and MMP. while BJP carried only the VL idiotype. The 30 kDa component, however, failed to react with antibody to either the μ, γ, α, K, or λ isotype, indicating that it had an Fv‐like molecular composition. These results suggest that myeloma cells of KK had diverged from the same precursor B cell clone to produce MPs of different isotypes and altered molecular constructions.

The effect of human C-reactive protein (CRP) on macrophage function was studied in an assay of superoxide anion (O2-) production. Peritoneal exudate macrophages (PEM) of guinea pigs exposed in vitro to various doses of CRP for 72 hr resulted in the development of O2-production dose-dependently, measured by increases in superoxide dismutase-inhibitable nitro blue tetrazolium reduction. The O2-producing activity of PEM cultured without CRP, used as a control, decreased markedly in proportion to incubation time. The O2-production by PEM exposed to CRP for 18 hr when control PEM were still high in O2-production, was decreased by larger doses of CRP, while PEM cultured without CRP for 72 hr, when production by control PEM was very low, followed by incubation with CRP for another 18 hr, produced O2-CRP-dose-dependently as in the case of that observed after 72-hr incubation with CRP. These results indicate that CRP is capable of activating macrophages and acts on macrophage function as a modulator. CRP possesses migration inhibitory factor (MIF)-like activity (as reported in the preceding paper) and also macrophage-activating factor (MAF)-like activity, indicating that CRP may play a functional role at the site of inflammation and tissue damage by accumulating and activating macrophages.

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The relationship between zinc sulfate turbidity test (ZTT) and thymol turbidity test (TTT), and IgG subclasses, especially IgG1 and IgG2, was studied. Serum colloidal reactions of specimens from patients with IgG‐myeloma usually show abnormally high values in ZTT and low values in TTT. But in some cases. values in ZTT and TTT are both low, and in a few cases both values are abnormally high. In order to see the reason why IgG‐myelomas are classified into these three groups according to serum colloidal reactions, IgG subclasses of monoclonal proteins (MPs) isolated by zone electrophoresis were determined by immunodiffusion with anti IgG‐subclasses. Results revealed that IgG1‐myeloma showed high ZTT and low TTT and IgG2‐myeloma showed low ZTT and TTT. Only two out of our 29 cases with IgG‐myeloma showed high ZTT and TTT. MP from one of them belonged to IgG1‐k and that from the other to IgG2‐λ. We checked the relationship between turbidity tests and electrophoretic mobility of MP and also that between these tests and L‐chains' type of MP, but did not find any relationship between them. These findings suggest that IgG1 innately reacts with ZTT but not with TTT, while IgG2 does not react with any of these tests. MP from cases showing high values in both ZTT and TTT may have a special idiotype.

Affinity-purified autoantibodies against nuclear ribonucleoprotein (nRNP) antigens were applied to fresh-frozen sections of benign tumors, carcinomas in silu, and carcinomas of the human skin. Using indirect immunofluorescence, the benign lesions showed speckled nuclear staining as seen in the normal epidermis. Invasive tumors such as basal cell epitheliomas and squamous cell carcinomas, in contrast, lacked im-munoreactivity for nRNP antigens. Recently, ribonucleoprotein complexes defined by nRNP antigens have been postulated to be involved in the excision of intervening sequences of premessenger ribonucleic acids (RNAs). Our findings provide useful information for the understanding of the pathophysiology of human skin cancers.