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Observations based on elution of IgG from nephritic kidneys of NZ mice and absorption of the eluted IgG with selected antigens indicate that their immune complex nephritis involves at least two kinds of antigen-antibody complexes. Antibodies reactive with nuclear antigens account for nearly half of the IgG eluted from the kidneys while antibodies reactive with Gross viral antigens make up a significant but lesser amount. Superimposed chronic viral infections affect the nephritis of NZ mice in different ways. LCM and polyoma infections hasten and intensify the antinuclear antibody responses and glomerulonephritis of these mice while LDV infection appears to protect against both antinuclear antibody formation and development of nephritis.

The amounts of BSA (immune complex) deposited in glomeruli of rabbits with acute and chronic serum sickness were determined using radio-labeled BSA and paired-label RSA. In animals with acute serum sickness and severe glomerulonephritis, about 18 microg of I*BSA were present in both kidneys after immune elimination (99% of the circulating I*BSA). Visible with an immunofluorescent sensitivity of 0.25 microg per g of kidney, the I*BSA became rapidly undetectable and was presumably covered by deposits of circulating host anti-BSA and complement which increased demonstrably. In chronic serum sickness produced by daily injections of a quantity of BSA to balance antibody production, 0.04% of the daily dose of I*BSA was deposited in the glomeruli during the developmental stages of glomerulonephritis. Coincident with the onset of overt proteinuric glomerulonephritis, the daily I*BSA deposition, rate increased to about 0.5% of the daily dose. The half-disappearance rate of I*BSA from the kidney was about 5 days. Administration of huge excesses of BSA caused a fivefold increase in the half-disappearance rate. The accelerated I*BSA disappearance could be correlated with vanishing glomerular immunofluorescent deposits of BSA and immunoglobulin, as well as electron microscopic dense deposits; however, functional improvement of the disease was not observed. The roles of immune complex size, precipitating and nonprecipitating (total ABC) antibodies, and RES function in the development of chronic serum sickness glomerulonephritis are discussed.

We report the generation and serologic, cellular, histologic, and genetic characteristics of a BXSB/MpJScr substrain, termed BXSB/MpJScr-ll/ll, that has lost early-life male lupus disease. Classic genetic analysis suggested that delayed disease expression results from the action of a single autosomal recessive gene. This putative gene, referred to as ll (long-lived), causes a significant delay in expression of autoimmune serology (total serum IgG and anti-nuclear antibodies levels), monocytosis, and of immune complex-mediated histopathologic changes such as glomerulonephritis, arteritis, and myocardial infarction. Presumably as a consequence of the delayed immunopathology male BXSB/MpJScr-ll/ll mice live three to four times longer than regular BXSB/MpJScr. This strain might be useful for analysis of single genes responsible for severe autoimmune disease expression.

A chimeric model consisting of severe combined immune deficiency (SCID) mice populated with human peripheral blood leukocytes (PBL) has recently been described (bu-PBL-SCID mice). These reports indicated a limited reconstruction of the transferred human immune system and functionality of the human graft. Herein we described modifications of the PBL transfer method that minimize transfer time and cellular manipulations, leading to a more effective population of SCID mouse recipients. Severe combined immune deficiency mice given 15 x 10(6) PBL had human IgG serum levels reaching 2 to 5 g/l, and all mice had detectable human anti-tetanus toxoid antibody levels when they received cells from donors with such levels. These transfers were associated also with clinical and histologic evidence of graft-versus-host disease, suggesting responsiveness of the human graft in the recipients. When Epstein-Barr virus seropositive (EBV+) donors were used, the chimeric mice also showed a high incidence of fatal lymphoproliferative disease 1 to 3 months after transfer of 15 x 10(6) PBL. The high level of immunoglobulin synthesis and immunoresponsiveness of the human cells with this transfer procedure may expand the use of these chimeric mice for the manipulations of human immune cells in vivo.

We present a 2-year serologic analysis of severe combined immune deficiency (SCID) mice populated with human peripheral blood leukocytes (PBL, hu-PBL-SCID mice). After 10-20 x 10(6) PBL transfer, human IgG serum levels generally increased in the SCID mouse recipient for 2 months, and thereafter decreased without returning to zero for at least 2 years. Great variability existed between different hu-PBL-SCID mice with regard to Ig serum levels even when derived from the same donor's PBL aliquot. The ratio of IgM to IgG serum levels was lower in hu-PBL-SCID mice than in the donors. The half-life of human IgG in the SCID mouse is shorter than in the human (8 days vs 23 days), suggesting a much higher production of IgG than expected from serum levels. The majority of hu-PBL-SCID mouse sera analyzed by high resolution electrophoresis had a smear appearance suggestive of diverse human Ig, generally with superimposed multiple faint mIg. Few mice developed strong human mIg, associated with lymphoproliferative diseases. In the hu-PBL-SCID mouse model, the transfer of cells from donors making antibody with defined specificity against TT and nuclear antigen resulted in the appearance of these antibodies in only a minority of the recipients.

The effect of neonatal thymectomy on the induction and/or modification of murine SLE disease was examined in several representative groups of mice with early-life SLE (MRL/Mp-lpr/lpr females, BXSB males, (NZB X W)F1 females, (NZW X BXSB)F1 males and females), late-life SLE (MRL/Mp-+/+ and BXSB females), and normal strains (BALB/c and C57BL/6 females). Our results indicated that thymectomy prevented disease only in the MRL/Mp-lpr/lpr SLE mice, and that this effect diminished as thymectomy was delayed beyond 3 wk post-natally. In the other SLE mice studied, neonatal thymectomy did not modify disease symptoms to any significant degree. Moreover, depletion of mature T cells from donor BXSB male bone marrow did not affect the expression of early-life SLE in thymectomized BXSB female recipients. Neonatal thymectomy did not induce SLE in normal mice. Of note, neonatal thymectomy did not completely deplete the Thy-1.2+ cell population, i.e., 10 to 15% remained in the spleens of the thymectomized mice. This incomplete T cell depletion, together with the previously demonstrated dependence on and hyperresponsiveness of BXSB and (NZB X W)F1 B cells to T helper cell-derived accessory signals, cast doubts on earlier conclusions that B cells from some SLE mice can autonomously proliferate and differentiate to autoantibody-secreting cells. It seems more appropriate to conclude that B cells from the various SLE mice vary in their degree of response to, and production of, T cell-derived helper signals, and thus in their expression of B cell hyperactivity and disease.

Previous studies of the genetic bases of murine SLE have defined gene segments that encode the H chain and the kappa L chain of anti-DNA, anti-Sm, and anti-IgG autoantibodies. As a result of these studies, the genetic origins of autoantibody H chains and kappa L chains are better understood, but little remains known about the genetic bases of autoantibody lambda-chains. Thus, we have analyzed serologically the germ-line and somatic origins of lambda 1 L chains in antibodies of normal mice and in both antibodies and autoantibodies of autoimmune mice. This study finds an increased lambda 1 diversity in both Ag-stimulated mice and autoimmune mice. This study also finds that the lambda 1 L chains in antibodies of unstimulated normal mice have the gene segment-encoded variable region, V lambda 1. In contrast, additional genetic processes appear to make the lambda 1 V regions of antibodies in Ag-stimulated normal mice and the lambda 1 V regions of both antibodies and autoantibodies in autoimmune mice. The increased lambda 1 diversity that we found in both Ag-stimulated mice and autoimmune mice might be caused by mutational processes creating antibody diversities. Therefore, the same somatic processes might be able to make both antibody and autoantibody lambda 1 diversities.

A common cellular abnormality of all murine strains prone to systemic lupus erythematosus (SLE) is an increased spontaneous polyclonal expansion of B cells. Our findings support the existence of this SLE-associated abnormality because the numbers of B lymphocytes secreting all the different IgG subclasses and IgM in spleens of all lupus-prone mice are elevated, compared to levels of normal splenic immunoglobulin-producing cells. We also report that 1) spontaneous polyclonal stimulation of immunoglobulin in autoimmune mice is preferential for subclass, and that the preferentially stimulated isotypes in each SLE strain consistently dominate both circulating and kidney-deposited immune complexes; 2) distinct patterns of isotype preference exist among the autoimmune strains determined by inherent B cell proliferative abnormalities or by B cell proliferation affected by thymus-derived lymphocytes; and 3) chronic administration of the TI B cell mitogen Lipid A in late-life SLE-prone mice induces an early-life glomerulonephritis with auto-antibodies of an isotype composition characteristic of those spontaneously produced by inherently abnormal B cells of early-life lupus mice.

Anti-Ig autoantibodies (rheumatoid factors, RF) have been implicated in the pathogenesis of human and murine rheumatoid arthritis as well as in the regulation of normal immune responses. Their genetic origin, clonal diversity, and inducing agents, and the relatedness between RF associated with disease and those occurring under physiologic conditions are not well understood. In this study, the genetic and clonotypic origin of 34 monoclonal IgM RF-secreting hybridomas from arthritic MRL-lpr/lpr and nonarthritic MRL-+/+ and C57BL/6-lpr/lpr mice was examined by RNA hybridization. For this purpose, we used probes for 10 VH and 13 Vk gene families as well as all JH and Jk gene segments. The majority of hybridomas expressed distinct Ig gene segment patterns and, hence, were clonally unrelated. Overall, a variety of different V and J gene segments were expressed in the hybridoma panel, suggesting that a large number of distinct genetic elements participates in expression of RF-like activity. RF from arthritic mice expressed Vk messages from the overlapping Vk22 and Vk28 gene families more frequently than did those from nonarthritic mice. RF from autoimmune MRL mice, both arthritic MRL-lpr/lpr and nonarthritic MRL-+/+, showed skewed JH4 segment usage, whereas those from C57BL/6-lpr/lpr preferentially expressed JH2.

Both sexes of the (NZW x BXSB)F1 mice developed an early systemic lupus erythematosus-like disease. In males, the disease resembled that in the BXSB male parent and was not affected by sex hormonal manipulation. In females, the disease duplicated that of (NZB x NZW)F1 females by virtue of a delayed onset and estrogen dependence. Autoantibody production, circulating Ig-bound gp 70 immune complexes, and deposition of Ig and gp 70 in the affected glomeruli were demonstrated in both males and females. The abnormally high incidence of degenerative coronary vascular disease with myocardial infarction, particularly in these F1 males, provides a useful model for the investigation of a possible immunologic component in coronary vascular disease.

In murine SLE, two different vascular lesions can develop. A necrotizing polyarteritis (NPA), exclusively found in MRL/I mice, is characterized by a dense infiltration of PMN and fibrinoid necrosis of the arterial wall. The second, a degenerative vascular lesion, occurs in a low incidence in all SLE mice, except the (NZW X BXSB)F1 (WBF1) male, in which its incidence is 100%. This lesion shows subendothelial deposits of immunoglobulins with minimal or no inflammatory or proliferative reaction. This degenerative vascular disease (DVD) is predominantly localized in the coronary arteries and is highly correlated with myocardial infarction. Serologic analysis revealed that NPA in MRL/I mice was associated with relatively late development of high levels of autoantibodies and circulating immune complexes; DVD in WBF1 mice was associated with an early onset of autoantibody production of a low magnitude that gave rise to a persistent low level of circulating immune complexes. Characterization of circulating immune complexes in MRL/I mice showed these complexes were mainly of intermediate size (7S-19S) and contained predominantly anti-DNA antibodies. In WBF1 mice, complexes were barely detectable and contained mostly anti-gp70 antibodies. Elution of kidneys showed that the major antibody deposited in MRL/I mice has an anti-DNA specificity, whereas in WBF1 animals, the major antibody was anti-gp70. Furthermore, a 10 times greater amount of immunoglobulins could be eluted from WBF1 hearts with DVD than from MRL/I and BXSB hearts. Additionally, we found that the lack of an inflammatory reaction in DVD was not because of a preferential deposition of noncomplement-fixing IgG1 antibodies nor could it be related to a defective inflammatory response, because WBF1 mice had an undiminished reverse passive Arthus reaction throughout their lives. It is concluded that NPA develops secondary to high levels of autoantibodies with a concomitant rise in immune complexes, whereas DVD is associated with sustained low levels of circulating immune complexes.

Murine lymphocytes cultured with frozen and thawed Rauscher murine leukemia virus 100,000 x G supernatants demonstrated increased 3H-thymidine uptake. The stimulatory capacity co-purified with the major envelope glycoprotein, gp70, and can be specifically removed from viral supernatants by absorption with anti-gp70 antibody-linked Sepharose. Cells from all strains tested, including strains prone to autoimmune disease (MRL/1, (NZB X W)F1, NZB, and BXSB), immunologically normal strains (DBA/2, C57B1/6, BALB/c, C3H and 129/J), genetic low responders to LPS (C3H/HeJ), and mice congenitally T cell deficient (BALB/Wehi nu/nu) were equivalently responsive to viral protein stimulation. The response peaked after 3 to 4 days of culture, and cells responded at that time after brief exposure to virus supernatants at the initiation of culture. When gp70 concentrations comparable to serum levels were used, both spleen and mesenteric lymph node cells were capable of responding with stimulation indices of between 5 and 10; whereas bone marrow cells responded poorly, and neither thymocytes nor cortisone-resistant thymocytes responded. Lymphocyte stimulation was not diminished by the depletion of adherent cells, and both T- and B cell-enriched populations responded.

Autoimmune disease in BXSB mice progresses more rapidly in male animals. We have investigated the cellular basis of this effect by transferring male and female bone marrow and spleen cells into male and female lethally irradiated BXSB recipients. The rate of development of disease was measured by the overall mortality rate, mortality from glomerulonephritis, and development of serologic abnormalities. We found that the pace of disease in the BXSB sex chimeras was determined entirely by the sex of the donor of the transferred cells. Lethally irradiated BXSB animals receiving male cells had rapidly progressive disease, whether the recipients were themselves male or female, whereas female-cell recipients of either sex had slowly progressive disease. The male-specific effect that accelerates autoimmune disease in the BXSB is thus not hormonally mediated, but rather is expressed in the hematopoietic stem cell populations.

The severe autoimmune disease from which BXSB males die at an early age (young) can be transferred into lethally irradiated female recipients by inoculating them with male spleen or bone marrow cells; similar recipients of female spleen or bone marrow cells develop the late-life disease typical of BXSB females. Using this syngeneic cell transfer model, we investigated the possible ability of female splenic and bone marrow cells to modulate the transferred male disease. We found that female spleen cells or the T-enriched subpopulation of such cells successfully retarded the transferred male disease, as observed by the decreased and delayed glomerulonephritis-associated mortality and lowered levels of serum IgG, autoantibodies, and immune complexes. Transfers of female bone marrow or thymus or female splenic T-depleted subpopulations were incapable of suppressing the accelerated male disease. These results indicate that abnormalities of the male spleen or bone marrow inocula responsible for the transferred early autoimmune disease can be modified by female spleen cells, in particular the female T cell component.

Activation/proliferation of mouse and human T and B cells is associated with expression and subsequent release of interleukin 2 receptors (IL 2R) into the milieu. The soluble form of IL 2R, at least in part, retains its ability to bind to IL 2 and to anti-receptor antibodies, but its exact structure remains unknown. Because systemic lupus erythematosus (SLE) is associated with T and B cell activation, we have used monoclonal anti-IL 2R antibodies in an ELISA to measure levels of IL 2R in sera of various lupus strains. High levels of the released receptor were found at an active clinical stage in sera of four autoimmune strains of mice homozygous for the lpr (lymphoproliferation) gene that causes T cell expansion, massive lymphoid organ enlargement, and promotes the autoimmune process. High levels were also found in lupus mice characterized primarily by B cell proliferation (BXSB males) and in (NZB X W)F1 mice characterized by T and B cell activation. Similarly high IL 2R serum levels could be induced experimentally in normal mice injected with immunostimulants such as bacterial lipopolysaccharide or Freund's complete adjuvant. The results indicate that IL 2R serum levels may provide a good marker of ongoing lymphoid cell activation/proliferation, and thus might be useful in the follow-up of patients with systemic autoimmune or other lymphoproliferative disorders. The biologic roles, if any, of the soluble form of IL 2R and its effects in normal and abnormal conditions remain to be determined.

The retroviral envelope glycoprotein, gp70 was measured in the serum of New Zealand Black (NZB) and SWR mice and the progeny of their crosses. The serum gp70 values segregated to "NZB-like" and "SWR-like" levels in these mice. A complex mechanism determined the inheritance of NZB-like serum gp70 levels. We found that the factors determining the expression of this retroviral protein were independent of the genes (Nzv-1 and Nzv-2) that determined the expression of infectious xenotropic virus. Autoimmune disease, including immune deposit nephritis could be dissociated from the degree of expression of serum gp70. By contrast, presence of circulating immune complexes and anti-DNA antibody did correlate with the development of nephritis in these crosses. A significant correlation was found between high grade expression of serum gp70 and the presence of lymphomas in these mice.

Two-hundred twenty-four hybridomas secreting monoclonal IgM rheumatoid factor (hIgMRF) derived from MRL-lpr/lpr, MRL-+/+ and C57BL/6-lpr/lpr autoimmune mice were analyzed with regard to IgG subclass and domain specificity, and some for VH gene expression patterns. Among these mice, only MRL-lpr/lpr develop arthritis. Clonotypes specific for each of the four mouse IgG subclasses and clonotypes reacting with more than one IgG subclass were identified. Although each panel contained several clonotypes, the predominant one differed in each strain (MRL-lpr/lpr, anti-IgG2a; MRL-+/+, combined anti-IgG2a and 2b; C57BL/6-lpr/lpr, anti-IgG1 or combined anti-IgG1, 2a, and 3). The IgG domains recognized by these monoclonals were defined with mutant Ig carrying IgG1 heavy chains that lacked either the CH1 or CH3 domains, variant Ig carrying hybrid IgG2b-2a heavy chains, and IgG fragments. Inhibition of hIgMRF binding to IgG substrates by protein A was also assessed. Most determinants were assigned to the CH3 domain, but determinants in the hinge region, CH2 domain, and in some instances, even in the Fab portion, could also be identified. Hybridization of cytoplasmic RNA from 35 classes of diverse IgG subclass specificity with VH gene probes representing seven of the approximately 10 VH families (7183, S107, Q52, J558, J606, 36-60, X24) indicated that approximately 90% of these clones expressed VH genes belonging to the large J558 gene family. The results indicate that murine IgMRF are extremely heterogeneous in IgG subclass and domain specificities; the genetic background influences RF specificity characteristics that may relate to pathogenicity; and considering the complexity of the J558 VH gene family and reported RF heavy chain assignments to additional VH gene families, it appears that VH genes encoding RF are diverse.

In the past few years several articles in professional journals (1, 2, 3) and numerous reports in the public press have claimed that antibodies in cows' milk are absorbed in active form via the human gastrointestinal tract. Further, it has been suggested that by using milk from appropriately immunized cows, this method of passive immunization may be employed with benefit in the treatment of such human diseases as pollen allergies. So attractive is this hypothesis that clinical trials of milk from ragweed pollen immunized cows have been conducted in ragweed sensitive patients without, however, any apparent benefit (4). In these clinical trials the lack of a relatively pure antigen makes it impossible to determine quantitatively the amount of antibody in the milk or in the subject's serum after ingestion of milk, so that all results must be based on subjective observations.

Summary and Conclusions The elimination from the blood of I131 labelled bovine gamma globulin has been followed in 75 rabbits under nine different experimental conditions, and the rate of elimination of this antigen has been found to be an early and sensitive manifestation of the immune response.

Rabbits immunized to several homologous renal antigens developed a variety of autoantikidney antibodies. Some of these antibodies reacted with the host's glomeruli and appeared to cause glomerulonephritis. Passive transfer of sera from some of these nephritic rabbits into normal, unilaterally nephrectomized rabbits led to the induction of nephritis. The production of autoantibody to glomeruli was transitory in most instances in spite of continued immunization. In some rabbits immunized to whole kidney homogenate, extracts or sediment, antibodies were found fixed to renal tubular basement membranes where an ultrastructural lesion was demonstrated. Rabbits also produced antikidney antibody apparently to tubular cytoplasmic components which did not fix to kidney in vivo and were of no pathogenetic significance. Immunization with autologous renal basement membranes induced a small autoantibody response in half the rabbits. This response was not associated with detectable renal injury.

Summary Rabbits injected with crude or partially purified fractions of normal autologous or homologous urine developed glomerulonephritis. Only those fractions of urine which contained soluble GBM antigens were nephritogenic. The nephritis was shown to be mediated by anti-GBM antibodies and could be transferred to previously healthy recipients with globulin eluted from nephritic kidneys.

The autoimmune disease of BXSB mice is markedly accelerated by a Y chromosome-associated male-specific factor. In order to investigate the mechanism of this effect, we castrated male and female BXSB mice at 10 days of age and compared the course of development of their autoimmune syndrome with that of sham-operated, sex-matched, littermate controls. Orchiectomy did not delay the early onset of fatal immunopathology in males, and oophorectomy did not exacerbate the indolent progression of morbidity in females. We conclude, therefore, that the male-specific effect that accelerates BXSB autoimmune disease is not hormonally mediated.

The autoimmune BXSB male mouse early in life displays a resistance to tolerance induction that is common with the other autoimmune strains (MRL/1, NZB x W, and NZB) whereas its female counterpart, which in early life is immunologically normal, is easily tolerized. The cellular basis for the BXSB male's resistance to tolerance induction with DHGG was investigated by using adoptive male-female cell transfer systems. We found that irradiated female recipients of male T-depleted bone marrow cells, plus either male or female thymus cells, resisted tolerance induction, had hyperactive splenic Ig-secreting cells, and developed early glomerulonephritis. Recipients of male thymic cells plus T-depleted female bone marrow cells could be tolerized, did not have enhanced Ig secretion, and did not develop glomerulonephritis. Furthermore, donor male T-depleted bone marrow cells--but not male thymic, female thymic, or female bone marrow cells--resisted induction of tolerance before their transfer to produce lymphoid chimeras.

In the MRL/l mouse, gp70 apparently plays a role as an autoantigen in the development of SLE. However, while gp70 may be an important pathogenetic element, it is not essential to MRL SLE, since elimination of most of the serum gp70 and virtually all of the immune complex gp70 from MRL/l-low gp70 congenic lines had no observable effect on the course or nature of the disease. Thus, while gp70 in the MRL/l mouse appears to be a convenient autoantigenic target when present in significant levels, in its absence the host appears capable of directing its aberrant immunologic responsiveness elsewhere with undiminished pathogenicity.

The age-dependent capacity of NZB and (NZB x NZW)F1 hybrid, BALB/c, DBA/2, C57BL/6 and C3H mice to generate T cell-mediated immune responses was assessed qualitatively and quantitatively by measuring the following effector functions: (a) the time course of alloreactive cytotoxic T-cell activity triggered in vitro was comparable for NZ and other mouse strains; cell reactivity generated in vivo against EL4 tumour cells was low in young (NZB x NZW)F1 mice and in DBA/2 mice but was comparable for older (NZB x NZW)F1, NZB and other mouse strains; (b) the time-dependent, vaccinia virus-specific, cytotoxic T-cell activity after systemic infection was similar for all mouse strains; (c) the T cell-dependent primary footpad swelling after local injection with lymphocytic choriomeningitis virus was within the same range for all mouse strains tested with respect to size and kinetics of the reaction; (d) the cell-mediated immune protection against Listeria monocytogenes after systemic infection revealed that NZ mice are, independent of age, more susceptible than C3H or C57BL/6 mice and comparable to A strain mice. Therefore, these responses in young, or clinically relatively normal older, NZB or (NZB x NZW)F1 strains that are affected by a lupus-like autoimmune disease did not differ markedly from the range of responses of other mouse strains of 2-14 months of age, which are not known to be similarly diseased. Thus, overall cell-mediated immunity of NZ mice as assessed quantitatively and kinetically in these functional models is within normal ranges. Possible T-cell defects may therefore be selective and either do not occur or were not detected in these models.

Inbred mouse strains vary considerably in their susceptibility to the chronic neurologic disease caused by WM 1504 E virus. Although all strains inoculated with the virus showed evidence of viral replication, those strains destined to develop chronic disease showed consistently higher titers of viral antigen in their sera and also in their tissues, particularly in the central nervous system, than did resistant strains. Studies of hybrids made by mating susceptible C57BR/cdJ and resistant C57BL/6J strains indicated that resistance is dominant and not sex linked. The major areas of injury included neurons in the anterior horn of the spinal cord, the dentate nucleus of the cerebellum, and other nuclei in the brain stem. Involvement of oligodendrocytes with associated primary demyelination was also noted. Tissue damage accompanied intense gliosis but was without leukocyte infiltration. Immunopathologic studies and parabiotic experiments suggested that tissue injury was likely due to primary direct viral effects. Further, thymus-insufficient nude mice developed this chronic neurologic disease.

We have used purified bovine conglutinin to develop a solid state radioimmune assay for immune complexes. Employing aggregated human IgG incubated with fresh normal human serum (complement) as a model for immune complexes, we have shown that our conglutinin assay is sensitive and highly specific for immune complexes that have fixed complement. The assay preferentially detects large complexes, is minimally influenced by monomeric IgG, and can be inhibited by high ionic strength, calcium chelation, and acetamido sugars. In addition, we have surveyed several hundred clinical sera from patients with various immunopathologic disorders and find evidence of immune complexes in some.

Electron microscopic determination of C-type virions in gut-associated and genital tract epithelia was made in various murine strains. The number of morphologically identifiable C-type virus particles varied more than 100-fold among strains, being high in all strains exhibiting immunologic disease, as well as several immunologically normal strains, and low in other immunologically normal strains. No relationship was seen between the number of virions found in epithelial and lymphoid tissues. There was, however, a direct correlation between numbers of virions in epithelial tissues and levels of serum gp70.