IgG class antibodies against human IgM were detected in a human subject up to a titer of 1:1024 against 5 of a group of 23 monoclonal Waldenstr-m macroglobulins. Inhibition studies confirmed at least one antigenic determinant shared by the 5 IgMs. The determinant was present on the ji chain but required tertiary structure for its full expression. Inhibition of the reaction between the antibodies to IgM and erythrocytes coated with 2 of the 5 IgMs was obtained at titers of 1:2 to 1:16 with 51.0% of 300 normal sera (85.2% of sera from 122 Caucasian, 26.1% of sera from 23 Negro, and 27.7% of sera from 155 Japanese individuals). This inhibition was independent of the serum IgM concentration. Family studies indicated that the determinant was inherited according to basic Mendelian laws and appears to be the first allotypic marker on human serum IgM. We have designated it Mm 1.Numerous studies have been reported on the inherited allotypic markers on the y-heavy chains of IgG molecules (Gm markers) and on K-type light chains (Inv markers) (1,2). An allotypic marker on the a-heavy chains of IgA molecules was studied with a human serum containing antibodies against one of a group of IgA myeloma proteins and erythrocytes coated with the specific IgA myeloma protein by the chromic chloride method (3). This marker was originally designated Am, and is probably identical to the marker Am2 on IgA2 molecules (4). It has been redesignated A2m1 with the discovery of its allele designated A2m2, by Van Loghem et al.(submitted for publication).Attempts by several laboratories over the past 10 years to detect IgM allotypic determinants by similar techniques have been less fruitful (5). Anti-IgM antibodies were detected in an earlier study in only 16 of 378 sera (4.2%), including subjects who had had multiple blood transfusions or several pregnancies (5). These antibodies were of low titer, directed in each case against only one of a group of 15 Waldenstrom macroglobulins, and slightly inhibited in two cases by some normal sera (6). We report here studies on a subject whose serum contained IgG-class antibodies in high titer against five of a group of 23 monoclonal IgM macroglobulins. Inhibition experiments indicated a specificity against one or more determinants shared by the five IgM proteins, and the evidence indicates that this shared determinant represents an inherited characteristic ("allotype"). MATERIALS AND METHODSThe chromic chloride method (6) was used to coat erythrocytes from a group 0, Rh-positive subject with purified proteins from a group including 23
Idiotypic antigenic determinants on human monoclonal immunoglobulins were studied by hemagglutination inhibition (HAI) by using human O Rh-positive erythrocytes coated with the proteins by the chromic chloride method. The rabbit antisera to the purified proteins required initial absorption with washed normal human erythrocytes and the hemagglutinating titer of anti-idiotypic antibodies after absorption varied from 1:1,300 to 1:328,000 for different antisera. Specificities against non-idiotypic V-region determinants, such as V-region subgroups, could not be demonstrated in the antisera. The HAI method is both sensitive, with inhibition detected at inhibitor concentrations of 0.001 mg/ml, and specific, since heterologous proteins did not produce significant inhibition. In studies with a single myeloma protein, inhibition was only obtained with the whole homologous protein and fragments thereof which contained the combining site, e.g., F (ab′)2 and Fab. HAI is a satisfactory method for studying idiotypic specificities in human monoclonal immunoglobulins and should permit analysis of sharing of specificities and should prove suitable for the detection of residual myeloma protein in the serum of patients with multiple myeloma during their response to therapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.