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Recently we have identified two monoclonal immunoglobulin M (IgM) proteins that bind Klebsiella polysaccharides. The lymphocytes of one of these patients (M.A.Y.) were available for study. A substantial proportion of the B lymphocytes isolated from this patient's peripheral blood also bound Klebsiella polysaccharides with a pattern of specificity identical to that of the monoclonal IgM, and reacted with an anti-idiotypic antiserum directed against this IgM. Stripping the surface immunoglobulin from these lymphocytes eliminated this reactivity. Although no plasma cells were detected in the freshly isolated peripheral blood lymphocytes of this patient, plasma cells binding Klebsiella polysaccharide appeared after 7 d of in vitro culture. This occurred regardless of whether the cultures were supplemented with autologous plasma, normal human plasma, or fetal calf serum. Pokeweed mitogen neither stimulated nor inhibited the in vitro differentiation of the monoclonal B lymphocytes into plasma cells. This differentiation was, however, abrogated by F(ab')2 fragments of anti-human IgM and by anti-idiotypic antibodies, as well as by the Klebsiella polysaccharide with which the monoclonal IgM reacted.

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The role of delta-positive cells in the immune response was studied by comparing the effects of treatment with allotype-specific IgD hybridoma antibody on homozygous BALB/c or SJL/J and heterozygous (BALB x SJL)F1 mice. Homozygous mice, injected from birth with the relevant anti-delta antibody, made primary or secondary immune responses to intravenously injected trinitrophenyl (TNP)-Brucella abortus, TNP-Ficoll, and TNP-keyhole limpet hemocyanin, which did not differ significantly from those of control mice, despite the fact that IgD+ cells were depleted and Ig+ cells were markedly reduced in the spleens of treated mice. Responses in nodes draining a local injection of TNP-Brucella abortus were, however, significantly suppressed. Heterozygous mice, injected from birth with either anti-Ig-5a or anti-Ig-5b, showed a marked reduction in the number cells producing IgG antibody of linked allotype specificity in the secondary response to intravenously injected sheep erythrocytes. A corresponding decrease in the amount of serum IgG2a of that allotype specificity was also noted. However, in agreement with the results obtained in homozygotes, heterozygotes injected simultaneously with anti-IgD directed against each of the allotypes made normal, if not enhanced, plaque-forming cell responses of both allotype specificities. Similarly, serum IgG2a levels were normal in all but one mouse treated in this fashion. These results indicate that IgD+ cells are not essential for an immune response in vivo. Although the delta-positive cell is used preferentially under normal conditions, it appears that an alternative mechanism exists by which, in the absence of these cells, the animal is able to make a normal immune response.

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Human IgD present in the serum of normal individuals or of patients with Hodgkin's disease (having high IgD concentrations) was characterized and compared with five IgD myeloma proteins. IgD was isolated using a highly specific anti-delta insoluble immunoabsorbent from which the bound material was eluted with sodium dodecyl sulphate (SDS) or urea. The latter reagent could be removed by extensive dialysis, thus making possible the renaturation of the eluted molecules. The purity of the IgD thus isolated was confirmed by antigenic analysis. Both kappa and lambda light chain determinants were present on serum IgD, although lambda light chain was predominant with a ratio over the kappa chain of 2:1. SDS-polyacrylamide slab gel electrophoresis analysis revealed two different molecular forms of serum IgD, one (IgD) migrating identically to monoclonal IgD, the other (IgD2) having a faster mobility. The difference between the two molecules was entirely, due to the different sizes of their constituent delta chains. Peptide mapping of the two chains (delta1 and delta2 respectively) and of the delta chain of an IgD myeloma protein was carried out using 125I-labelled material. The three molecules displayed a high degree of homology, the delta2 chain differing by the presence of three characteristic extra peptides. The significance of these extra peptides is discussed in the light of the peptide mapping technique employed.

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Serum IgD concentrations have been determined in twenty-one patients with Hodgkin's disease, in eight patients with non-Hodgkin's lymphomas and in twenty-eight normal (control) individuals by both a solidphase radio-immuno-assay and radial-immunodiffusion. Fourteen of the Hodgkin's patients displayed three to forty-five-fold increased serum IgD levels as compared to control individuals, while in the remaining seven patients IgD concentrations were practically normal. Patients with non-Hodgkin's lymphomas had decreased IgD concentrations.

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The specificity of the IgM receptor expressed by human T cells cultured in IgM-free media has been investigated. IgM receptors have been detected using a rosette system with ox erythrocytes coated with rabbit antibody (EA(IgM)), and the inhibitory capacity of different IgM fragments in the rosette system has been tested. It was found that F(c)5mu but not F(ab')2mu, nor monomeric IgM (8 S IgM) inhibited EA (IgM) rosette-forming cells. This indicates that the receptor present on the surface of T cells has affinity for a structure located in the Fc portion of the pentameric IgM.

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