A human monoclonal macroglobulin with specificity for alpha(2----8)-linked poly-N-acetyl neuraminic acid, the capsular polysaccharide of group B meningococci and Escherichia coli K1, which crossreacts with polynucleotides and with denatured DNA.

We have described an IgM antibody from a patient with macroglobulinemia specifically reacting with poly-alpha(2----8)N-acetyl neuraminic acid (NeuNAc) the capsular polysaccharide of two important human pathogens, group B meningococcus and E. coli K1. This antibody has a narrowly defined specificity in its interactions with polysaccharides, being unable to bind poly-alpha(2----9)NeuNAc or alternating poly-alpha(2----8)alpha(2----9)NeuNAc. However, it shows interesting crossreactivity with seemingly unrelated polynucleotides and denatured DNA, supporting the hypothesis that charged groups with a given spacing may determine the specificity of antigen-antibody interactions on otherwise dissimilar molecular structures. Despite the crossreactivity with denatured DNA and polynucleotides, the antibody does not appear to have adverse effects in the patient. The antibody protects newborn rats against E. coli K1 infection, as well as the standard horse antiserum H46, and one would expect it to prove useful in humans as an adjunct to antibiotic therapy in infections with group B meningococcus and E. coli K1. We have attempted to clone the antibody-producing cells from peripheral blood, and have shown that the relevant cells are present and can be cultured.

THYMUS-DEPENDENT LYMPHOCYTES IN TISSUE SECTIONS OF REJECTING RAT RENAL ALLOGRAFTS

Lewis kidneys were grafted into BN recipients and examined at daily intervals up to 6 days after grafting with immunofluorescent reagents. A horse antiserum specific for T lymphocytes revealed an increasing number of T lymphocytes in the cellular infiltrates of rejecting allografts. These were detectable 1 day after grafting, reached a maximum 3 days later, and were relatively diminished at 6 days. In control isografts and nonimmunological inflammations of kidney, a small number of dispersed T lymphocytes was seen. A rabbit antirat thymocyte antiserum, given to allografted BN rats, prolonged survival of the grafts and decreased the cellular infiltrate and the number of T lymphocytes in the infiltrates. We conclude that in graft rejection there is a flow of T lymphocytes into areas of tissue damage and these T lymphocytes are immunologically reactive to graft antigens.

PAPAIN-PRODUCED FRAGMENTS OF HORSE γ- AND β-GLOBULIN ANTITOXINS

Preparations consisting mostly of γ- or β-globulin were obtained from a horse antiserum to diphtheria toxin by ammonium sulfate precipitation. These preparations were treated with papain and the digests separated on Sephadex G-100 columns. The γ-globulin digests were resolved into a major 3.4 S component and smaller minor components. The β-globulin digest contained similar fragments and, in addition, a major 5.0 S component. All fragments neutralized toxin, the most active being the β-globulin 5.0 S and 3.4 S fragments. The 3.4 S γ- and β-globulin fragments were univalent. The 5.0 S β-globulin fragment was divalent, and it could be reduced to 3.4 S subunits by treatment with 0.3 M 2-mercaptoethanol.