Idiotypic analysis of a B cell clone with anti-intermediate filament specificity in a patient with Sjögren's syndrome: involvement of five subpopulations producing different immunoglobulin isotypes.
An IgM paraprotein from patient LP with Sjögren's syndrome exhibited an antibody activity to intermediate filaments (IMF) of cells from all vertebrates examined, and appeared to recognize several classes of IMF (i.e., vimentin, desmin, and keratin). A mouse monoclonal anti-idiotype (Id) antibody, K4A, was prepared against the IgMk (LP) and used as a specific probe in two-color immunofluorescence to examine the extent of clonal involvement in the patient's blood and bone marrow mononuclear cells (MNC). Twenty to 30% of MNC in her blood samples were IgMk+ plasmablasts with morphologic similarity to Waldenström's macroglobulinemia cells. IgG+ and IgA+ plasmablasts were demonstrated in lower frequencies (approximately 2%). Almost all of the IgM+ cells and approximately 80% of the IgG+ cells and IgA+ cells in the blood were reactive with the K4A anti-Id antibody. Immunoglobulin (Ig) subclass analysis revealed that the K4A Id was expressed by IgG1+, IgG3+, IgA1+ and IgA2+ plasmablasts. Similar observations were obtained with bone marrow samples, although the proportion of Id+ cells among IgG+ or IgA+ cells was lower in marrow than in blood. IgG and IgA fractions isolated from the patient's serum were also shown to contain anti-IMF activity. Ig biosynthetic analysis of blood MNC revealed that the K4A anti-Id antibody precipitated not only IgM but also IgG and IgA. Because cells simultaneously producing two different Ig isotypes were not detected, these results indicate the presence of five separate subpopulations of the K4A Id+ neoplastic clone. The data thus suggest the occurrence of a neoplastic or pre-neoplastic transformation event before the switching of Ig heavy chain isotypes, and imply a role for the IMF antigen in the exaggerated proliferation and differentiation along five of the nine potential intraclonal pathways.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis; D000918:Antibody Specificity; D001323:Autoantibodies / Q000032:analysis; D001402:B-Lymphocytes / Q000145:classification* / Q000276:immunology; D002999:Clone Cells / Q000145:classification / Q000276:immunology; D003599:Cytoskeleton / Q000276:immunology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007126:Immunoglobulin Allotypes / Q000032:analysis* / Q000145:classification; D007130:Immunoglobulin Idiotypes / Q000032:analysis* / Q000276:immunology; D007075:Immunoglobulin M / Q000032:analysis; D007145:Immunoglobulin kappa-Chains / Q000032:analysis; D007382:Intermediate Filaments / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010266:Paraproteins / Q000032:analysis; D051381:Rats; D012859:Sjogren's Syndrome / Q000276:immunology*; D013552:Swine
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007126:Immunoglobulin Allotypes; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D010266:Paraproteins