ovalbumin and Hypergammaglobulinemia

IgE hyperproduction frequently observed in patients with atopic dermatitis (AD) may greatly contribute to the pathogenesis of AD, but its mechanisms are still unclear. NC/Nga mice raised in nonsterile circumstances spontaneously suffered from AD-like skin lesions with elevation of plasma IgE levels. We investigated mechanisms of the IgE hyperproduction in NC/Nga mice. Splenic T cells from SPF NC/Nga mice had a level of CD40 ligand (CD40L) expression comparable to that of BALB/c mice. Although there was no difference in the expression of CD40 on B cells between NC/Nga and BALB/c mice, B cells of NC/Nga mice produced much more IgE in the presence of soluble CD40L and IL-4. The stimulation with CD40L and/or IL-4 resulted in tyrosine phosphorylation of Janus kinase 3 (JAK3) in B cells, which was more strongly inducible in NC/Nga mice than in BALB/c mice. In B cells isolated from PBMC of AD patients with high serum IgE levels, JAK3 was constitutively phosphorylated at the tyrosine residue, and its phosphorylation was enhanced by the treatment with CD40L and/or IL-4 as was that in splenic B cells of NC/Nga mice with dermatitis and high IgE levels. Thus, it is suggested that constitutive and enhanced JAK3 phosphorylation in B cells highly sensitive to CD40L and IL-4 may be attributable to IgE hyperproduction in NC/Nga mice and patients with AD.

Topics: Aluminum Hydroxide; Animals; B-Lymphocytes; CD4-Positive T-Lymphocytes; CD40 Antigens; CD40 Ligand; Cells, Cultured; Coculture Techniques; Dermatitis, Atopic; Disease Models, Animal; Dose-Response Relationship, Immunologic; Humans; Hypergammaglobulinemia; Immunization; Immunoglobulin E; Immunoglobulin G; Interleukin-4; Janus Kinase 3; Ligands; Lymphocyte Activation; Male; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Mice, Inbred Strains; Ovalbumin; Phosphorylation; Protein-Tyrosine Kinases; Thy-1 Antigens; Tyrosine

368 1- to 5-year-old mink of wild-type or black genetic background were infected with Aleutian disease virus (ADV) naturally or using virus-containing immune complexes or purified virus. Thirty of the mink were immunized with dinitrophenol-conjugated ovalbumin (DNP-OA) before and during infection. Blood samples were taken at monthly intervals. We found that weak (and transient) monoclonal or oligoclonal immunoglobulin components were present in the plasma or serum approximately 1 month after infection, as judged by zone electrophoresis. In a few cases, we found quite stable myeloma-like hypergammaglobulinemia, which usually occurs much later in the infection. All sera with monoclonal immunoglobulin components and most of the sera with immunoglobulins of restricted heterogeneity were analysed by crossed serum line immunoelectrophoresis. In all cases, the distinct immunoglobulins were found to have antibody activity to ADV proteins. In the few sera from DNP-OA-immunized mink showing restricted immunoglobulin heterogeneity, this was also the case. The findings from the study imply that ADV-specific B lymphocytes are probably the primary targets for ADV. The resulting ADV replication introduces a "pseudo-transformation" stage, so that the infected B lymphocytes proliferate and differentiate to an extreme degree. The mechanism behind this B-cell pseudotransformation ability of ADV is a puzzle. It may, however, be important, that the p75/85 structural polypeptides of ADV contain an amino acid sequence almost identical to the GTP-binding pocket of the Ras oncogene.

Topics: Aleutian Mink Disease; Aleutian Mink Disease Virus; Amino Acid Sequence; Animals; Antibodies, Viral; B-Lymphocytes; Cross Reactions; Dinitrophenols; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Female; Genes, ras; GTP-Binding Proteins; Hypergammaglobulinemia; Immunoelectrophoresis; Immunoglobulin G; Male; Mink; Molecular Sequence Data; Ovalbumin; Sequence Homology, Nucleic Acid

This report is of seven-year-old girl with a lifelong history of severe eczema, intestinal features of food allergy, recurrent respiratory tract infections, chronic bilateral keratitis and mucocutaneous candidiasis. Immunological tests showed high serum IgE levels, with specific IgE antibodies to cow's milk and egg white, defective PMN chemotaxis and a marked defect in both the function and number of T-lymphocytes. On a cow's milk-free and egg-free diet the eczema subsided and the respiratory infections improved. A partial correction of the immunodeficiency was also observed. The relationships between the immune system and atopy are discussed.

Topics: Animals; Antibody Formation; Cattle; Chemotaxis, Leukocyte; Child; Eggs; Eosinophilia; Female; Food Hypersensitivity; Humans; Hypergammaglobulinemia; Immunity, Cellular; Immunoglobulin E; Milk; Ovalbumin