Abnormal binding of soluble IgG immune complexes to hepatic nonparenchymal cells of autoimmune mice

Because the liver is the major organ responsible for removal of soluble immune complexes (IC), the surface binding characteristics of preformed model IC to unstimulated mouse liver nonparenchymal cells (NPC) in suspension were studied. NPC of non-autoimmune C3H/FeJ, C3H/HeJ, A/J, DBA/2 and the autoimmune NZB/W F1 and MRL/lpr female mice of various ages were isolated by perfusion of the portal vein with collagenase followed by separation of NPC from hepatocytes with a metrizamide gradient. Thirty-five percent of NPC of all mouse strains were nonspecific esterase-positive and phagocytosed latex beads. Radiolabeled mouse IgG anti-DNP covalently cross-linked stable IC were separated by gel filtration and bound to NPC under various conditions. Marked differences were noted in maximal number of IC bound per cell between the autoimmune and non-autoimmune mouse strains: 3.3 to 4.0 X 10(5) in the non-autoimmune strains vs 0.3 to 1.4 X 10(5) molecules of IC bound per cell in the autoimmune strains at 1 to 6 mo. Insignificant differences were noted in Ka by Scatchard plot analysis (3.5 to 5.0 X 10(8) M-1) and rate of reversibility of binding as determined by dissociation of surface-bound IC with an excess of heat-aggregated gamma-globulin (T 1/2:1.5 to 2 min). These data demonstrate a decreased number of available binding sites for IC in unstimulated NPC from NZB/W F1 and MRL/lpr female mice throughout their life spans. Although the findings are consistent with saturation of binding sites of the NPC with native IC, the abnormality found in the 1-mo-old autoimmune mice (who do not have detectable autoantibodies) suggests a primary defect in FC receptor expression or an altered state of activation of NPC that may contribute to the disease process.     

Comparison of stem-cell recovery in autoimmune and normal strains

The capacity of NZB stem cells to proliferate in vivo was evaluated in two systems which required repopulation of peripheral organs. In both types of depletion systems, stem-cell repopulation after cyclophosphamide treatment or adoptive transfer repopulation in lethally irradiated hosts, it was found that NZB stem cells were hyperproliferating. The increase in proliferating cells was most pronounced in the spleens of NZB mice treated with high-dose cyclophosphamide and in lethally irradiated F₁ mice reconstituted with NZB T-cell-depleted bone marrow. Thus, upon a stimulus to repopulate, NZB marrow stem cells will hyperproliferate in peripheral organs resulting in an increase in cell number. The abnormality in the marrow cells can be observed in young NZB mice when their marrow cells are in an environment which requires recovery and division.     

Structural studies of an Inv (1, −2) kappa light chain

A Bence Jones protein with phenotype Inv (1, –2) was isolated from the urine of a patient with multiple myeloma. Inv typing of the patient's relatives established the presence of anInv ¹ allele in the kindred, and that the patient's genotype wasInv ¹/Inv ³. Hence, the absence of Inv (2) in the Bence Jones protein was shown to be genetic and not an artifact caused by the disease. The tryptic peptide-containing residues 191 through 194 were isolated and shown to be composed of Leu, Tyr, Ala, Cys, with Leu at the amino end. Hence, the residue at 191 is the same as that present in Inv (1, 2) Bence Jones proteins. More detailed study of the tryptic peptides established that residue 153 is Val rather than Ala as in all other K chains thus far studied. The primary sequence: Ala¹⁵³, Leu¹⁹¹ determines Inv (1, 2); Ala¹⁵³, Val¹⁹¹ determines Inv (3); and Val¹⁵³, Leu¹⁹¹ determines Inv (1). The Val¹⁵³, Val¹⁹¹ sequence has not been observed. It may correspond to Inv (–). These data are strikingly similar to the data for the Kern and Oz isotypes (changes at 154 and 191, respectively) in the chain. As in the case of theK chain, only three of the four possible combinations have been observed. The implications of this parallelism and of crystallographic findings on chains, reported by others, are discussed.     

Growth rate stimulation of marine pseudomonads by thiosulfate

The oxidation of thiosulfate to tetrathionate exerts a definite growth rate stimulation in glucose, acetate, and yeast extract cultures of some marine pseudomonads. The failure to find this effect in earlier studies with terrestrial isolates may lie in the particular conditions used in the present experiments (constant pH, high ratio of thiosulfate to organic substrate) or in the different metabolic characteristics of the marine isolates.Contribution No. 3220 from the Woods Hole Oceanographic Institution.