T- and B-Cell Functions in IgA-Deficient Patients

In vitro lymphocyte function of 60 IgA-deficient patients (IgAdp) were studied. In the mitogen-induced lymphocyte activation test, peripheral blood mononuclear cells (PBMC) of IgAdp showed a weaker response to pokeweed mitogen (PWM) than those of controls (P less than 0.05), and the responses to phytohaemagglutinin (PHA) and concanavalin A (Con A) were normal. The amounts of IgA, IgG, and IgM secreted by PBMC from controls and IgAdp were measured in vitro by enzyme immunoassay. B cells were activated by PWM with or without hydrocortisone (HC) to inhibit HC-sensitive suppressor cells. Lymphocytes of IgA-deficient patients synthesized only minute amounts of IgA in vitro and the amounts of IgA synthesized correlated well with the serum IgA levels. Both IgG and IgM secretion by PWM-stimulated PBMC of IgAdp were also subnormal. The lymphocyte subset analysis in the peripheral blood revealed normal numbers and ratios of T cells, but IgAdp had reduced percentages of surface IgA-bearing cells. Co-culture experiments with isolated B cells, CD4- and CD8+ cells from IgAdp. and controls showed low B-cell capacity for IgA production as the most constant finding. Defects in T-cell functions or changes in the proportions of surface antigen-carrying lymphocytes (other than IgA-) were infrequent and were not associated with any particular group of patients or type of IgAd (primary, acquired, or transient).     

B lymphocyte function in patients with rheumatoid arthritis: impact of regulatory T lymphocytes and macrophages--modulation by antirheumatic drugs

The present work analyses B lymphocyte functions in vitro in patients with rheumatoid arthritis (RA). The impact of gold salts and penicillamine on human B lymphocyte function in vitro is discussed. Synovial fluid monocytes/macrophages increased both the polyclonally induced and the antigen-induced blood lymphocyte proliferation and increased the numbers of immunoglobulin-secreting blood B lymphocytes generated by pokeweed mitogen (PWM), a T cell-dependent polyclonal activator. The lymphostimulatory factor(s) interleukin-1, which can be produced by monocytes/macrophages, was found in most cell-free synovial fluid specimens, but only in a few paired serum samples. Thus, in vivo activated synovial monocytes/macrophages may modulate lymphocyte functions. Compared to blood, synovial fluid T lymphocytes comprised fewer T4+ (helper/inducer) cells and more T8+ (suppressor/cytotoxic) cells. Synovial fluid lymphocytes proliferated poorly when stimulated polyclonally. However, the proliferative responses to microbial antigens as well as the lectin-induced lymphokine production equaled those of blood lymphocytes. In about half of RA patients, T4+ cells from synovial fluid increased the PWM-induced immunoglobulin secretion by autologous blood B lymphocytes to higher levels as compared to similar experiments with blood T4+ cells. Synovial fluid T8+ cells suppressed PWM-induced immunoglobulin production of autologous mononuclear cells to the same degree as seen with blood T8+ cells. A large proportion of synovial fluid T subsets expressed Ia antigens, probably due to in vivo activation. Thus, synovial T helper/inducer and T suppressor/cytotoxic cells may modulate the functional activities of synovial B lymphocytes. Among mononuclear cells isolated from synovial fluid and synovial tissue, considerable numbers of B lymphocytes spontaneously secreting IgG were found; fewer B cells secreted IgM and IgA. Rheumatoid factor activity was noted in about 7% of the IgG-producing cells. Synovial fluid mononuclear cells did not produce immunoglobulins in cultures stimulated with PWM, unless synovial T cells were removed and replaced with autologous blood T cells. Under these conditions synovial fluid B lymphocytes were induced by PWM to considerable IgG synthesis; fewer cells secreted IgM and IgA. About 8-9% of the induced IgM- and IgG-synthesizing cells displayed rheumatoid factor activity. Aurothiomalate markedly inhibited PWM-induced immunoglobulin production by normal lymphocytes cultured in vitro, probably by affecting monocyte/macrophage-lymphocyte interactions. The drug also had a direct inhibitory action on B lymphocytes, whereas T cells were resistant.(ABSTRACT TRUNCATED AT 400 WORDS)     

The effect of phenytoin in vitro on normal human mononuclear cells and on human lymphoblastoid B cell lines of different Ig isotype specificities

The anticonvulsant drug phenytoin, in less than cytotoxic concentrations, caused significant reductions in Ig secretion by unstimulated or EBV-stimulated normal MNC, as measured by PFC or secretion of Ig into the culture medium. Isotype-specific LBL varied in their sensitivity, the secretion of IgA (1 line) and IgG (3 lines) being reduced by phenytoin near therapeutic concentrations, whereas that of IgM (1 line) was resistant. Six-day exposure of MNC to phenytoin caused no selective depletion of or enrichment for B cells, monocytes or T cell subsets. The results suggest that the reduction in serum Ig levels reported in phenytoin-treated epileptic patients is, at least in part, due to a direct effect of the drug on the B lymphocyte. However, among EBV-activated normal MNC, those secreting IgA were no more sensitive to the drug than those secreting IgG or IgM, and other factors may, therefore, operate to cause the preferential reduction in serum IgA in phenytoin-treated patients.     

Epstein-Barr virus-induced immunoglobulin synthesis by B cells from individuals with late-onset panhypogammaglobulinemia

Epstein-Barr virus (EBV) transformation was used to examine the differentiation potential of circulating B cells from eight individuals with late-onset panhypogammaglobulinemia. Cytoplasmic and secreted immunoglobulins were evaluated by immunofluorescence and radio-immunoassay. EBV-infected cultures of B cells from patients and healthy controls generated similar numbers of IgM-secreting plasma cells, but relatively few IgG and IgA plasma cells were induced in cultures of patients' B cells. As further evidence of B-cell immaturity, approximately 90% of the IgA B cells in the eight patients coexpressed IgM. Clonal diversity of B cells from hypogammaglobulinemic patients was examined with a panel of mouse monoclonal antibodies directed against idiotypic and V_H subgroup determinants. The frequencies of EBV-induced plasma cells exhibiting the different idiotypic and V_H determinants were similar for patients and controls. The data suggest the continued generation of clonally diverse B cells that are capable of terminal plasma-cell differentiation when the normal triggering mechanisms are bypassed by EBV. The arrested differentiation at an immature B-cell stage in these hypogammaglobulinemic individuals would appear to reflect a defect in normal B-cell triggering.     

Circulating and pokeweed mitogen-induced immunoglobulin-secreting cells in systemic lupus erythematosus.

Peripheral blood mononuclear cells (PBM) obtained from patients with active untreated systemic lupus erythematosus (SLE) were evaluated both for the number of cells spontaneously secreting immunoglobulin (Ig) as well as for their capacity to generate immunoglobulin-secreting cells (ISC) in vitro in response to pokeweed mitogen (PWM). ISC were enumerated by a reverse haemolytic plaque assay designed to quantify the number of cells secreting IgG, IgM and IgA. PBM obtained from eight patients with active untreated SLE contained markedly increased numbers of ISC compared to age-, sex-, and race-matched normal control PBM. SLE PBM contained a mean of 13,805 +/- 3266 ISC per 10(6) cells, of which 74% secreted IgG, 10% IgM and 22% IgA, while normal PBM contained a mean of 779 +/- 143 ISC per 10(6) cells, with 57% secreting IgG, 25% IgM and 33% IgA. PBM obtained from SLE patients were also examined for their ability to generate ISC in vitro in response to PWM. SLE PBM were markedly deficient in their capacity to respond to PWM with the differentiation of ISC. This diminished responsiveness could not be ascribed to serum factors, the presence of increased numbers of cells with suppressive capacity or the absence of potentially responsive B cells. Rather, a deficiency of helper T cell activity appeared to be responsible. This was indicated by the observation that PWM responsiveness could be restored to SLE PBM by co-culturing them with purified mitomycin C-treated normal T cells.     

Selective enhancement of human IgE production in vitro by synergy of pokeweed mitogen and mercuric chloride

IgE production in vitro was investigated in cultures of human peripheral blood mononuclear cells (MNC) from non-atopic donors with pokeweed mitogen (PWM), mercuric chloride (HgCl2), or both. PWM alone induced a few IgE immunoglobulin secreting cells (ISC) detected by reverse plaque forming cells (PFC) and many IgG, IgM, and IgA PFC. HgCl2 alone failed to produce significant numbers of ISC of any class. PWM plus HgCl2 caused a selective increase of IgE PFC without affecting IgG, IgM, and IgA PFC. Co-cultures of B cells plus mitomycin C (MMC) treated T cells stimulated by PWM alone produced more IgG, IgM, IgA and IgE PFC than those of B cells plus T cells. However, PWM plus HgCl2 produced significantly more IgE PFC selectively in those cultures. This effect was observed in the cells of most of the donors, but a few donors showed different responses.     

J chain synthesis in lymphocytes from patients with selective IgA deficiency.

J chain synthesis was investigated by in vitro pokeweed mitogen (PWM) stimulated peripheral blood lymphocyte (PBL) cultures in eight patients with selective IgA deficiency and compared with that of normal persons. In normals, all IgM-containing cells always had the J chain but only in a portion of IgG- and IgA-containing cells was J chain detectable. The percentage of J chain-positive cells amongst IgG or IgA cells increased during culture, reached a peak at days 5-6 or 6-7, respectively, and then decreased. IgA-deficient patients had very few IgA-containing cells and an increased number and percentage of J chain-positive IgG cells, except for one patient, who had a significant number of IgA-containing cells without IgA secretion into the culture supernatants. Measurement of Ig in culture supernatants by radioimmunoassay revealed that lymphocytes from seven patients secreted significantly smaller amounts of IgG and IgM than did the normal controls, in addition to the defect in IgA production. These results suggested the presence of some ontogenetic relationship between J chain-positive IgG cells and the precursors of IgA-producing cells, and some functional immaturity of most IgG-producing clones seen in patients with selective IgA deficiency.     

Polyclonal Activation of Human Peripheral Blood B Lymphocytes by Formaldehyde-Fixed Salmonella paratyphi B

B-cell 'activation' in cultures stimulated with pokeweed mitogen (PWM), Staphylococcus aureus strain Cowan I, or formaldehyde-fixed Salmonella paratyphi B (SPB) was evaluated by enumeration of cells secreting immunoglobulin (Ig) and by quantitation of Ig released into culture supernatants. A dissociation between these two values was found after day 6 in cultures activated with PWM or SPB, suggesting that Ig-secreting cells (ISC) are heterogeneous in terms of Ig secretion rate. Generation of ISC in cultures activated with PWM or SPB was partially inhibited by hydroxyurea, but [g levels in culture supernatants were not affected. These results indicate that there are at least two subpopulations of ISC in stimulated peripheral blood lymphocyte cultures, one sensitive to, and the other resistant to, hydroxyurea. The hydroxyurea-resistant subpopulation appeared to be more mature and to release almost all of the Ig detected in culture supernatants. Furthermore, time-course studies of ISC numbers and Ig levels showed that each ISC in SPB-stimulted cultures (but not in PWM-stimulated cultures) was more active in Ig synthesis and secretion after day 8 than before day 6, indicating that after day 8 most of the ISC in cultures activated with SPB were hydroxyurea-resistant. These studies suggest that SPB is another useful polyclonal B-cell 'activator' for studies of human B-cell differentiation and function, and that SPB defines two distinct subsets of B cells.     

Defective in vitro immunoglobulin production in response to pokeweed mitogen in patients with Hodgkin's disease pretreatment and in remission

In vitro production of IgG and IgM from peripheral blood lymphocytes and B-cell enriched fractions was assessed in a group of Hodgkin's disease (HD) patients and normal controls using pokeweed mitogen (PWM) stimulation. Our studies demonstrated a significant (P less than 0.01) reduction in the absolute number of helper (OKT4 positive) T cells and a significant alteration in the helper/suppressor T-cell ratio (0.89 +/- 0.15) compared to normal (1.83 +/- 0.31). Results from PWM stimulation experiments demonstrated that HD patients produced significantly lower IgG (P less than 0.01) and IgM (P less than 0.01) levels than controls. Synthesis of IgM but not IgG induced by PWM was subnormal after addition to patient B-cell cultures of autologous irradiated T cells or allogeneic irradiated normal T lymphocytes. Irradiated T cells from HD patients were as effective as normal T cells in helping PWM induced IgG and IgM synthesis by normal B cells. Our results suggest that in HD impaired circulating B-cell function is partly due to T-suppressor cell activity and furthermore that B-cell subpopulations producing different immunoglobulin isotypes may either be defective or vary in their susceptibility to T-cell suppression.     

Immunological and purine enzyme studies on hyperuricaemic and normouricaemic patients with Down''s syndrome.

Hyperuricaemia in Down's syndrome is unreleated to the activity of phosphoribosylamidotransfrease, which catalyses the activity of the first specific step on the purine biosynthetic pathway, and to the activity of hypoxanthine phosphoribosyltransferase and phosphoribosylpyrophosphate synthetase, abnormalities of which are known to be associated with hyperuricaemia. Immunological studies involving serum immunoglobulins, natural E. coli antibodies, test immunization with pneumococcal polysaccharide type III (PnPS), in vitro lymphocyte transformation to mitogens, and pokeweed mitogen (PWM) induced immunoglobulin production showed no difference between hyperuricaemic or normouricaemic Down's patients and institutionalized controls. The Down's patients had higher serum IgA, IgG and IgE, and some also produced more immunoglobulin in PWM-stimulated lymphocyte cultures when compared to normal healthy controls. However, both patients with Down's syndrome and the institutionalized controls had significantly lower responses to PnPs than normal healthy controls. The only deficiency confined to the Down's patients was a signficant depression in delayed hypersensitivity to dinitrochlorobenzene. These findings indicate that the in vivo abnormality of depressed cellular and humoral immunity in Down's patients is not paralleled by in vitro function as measured by PHA lymphocyte transformation and immunoglobulin production by PWM-stimulated lymphocytes. There is also no apparent link between a putative defect in purine metabolism in Down's patients and any immunological abnormalities.     

Evidence that Pokeweed-Mitogen-reactive B Cells are Pre-committed in Vivo to the High-rate Secretion of a Single Immunoglobulin Isotype in Vitro

Normal human peripheral blood B cells that respond to pokeweek mitogen (PWM)-activated irradiated T cells with high-rate immunoglobulin secretion in vitro were analysed with respect to the frequency of the cells stimulated to high-rate immunoglobulin secretion in vitro and whether the progeny of each cell had the potential to secrete one or multiple immunoglobulin isotypes. In vitro cultures containing limiting numbers of human B cells were initiated in the presence of PWM and excess irradiated T cells, and the quantity of IgM, IgG and IgA secreted was determined after 9 days. The level of immunoglobulin secretion per cell in limiting-dilution microcultures was shown to be equivalent to that seen in the routinely used macrocultures, indicating that major loss of B-cell function was not occurring in the microcultures. At limiting B-cell numbers, individual microcultures were of ten shown to produce immunoglobulin of a single isotype, either IgM, IgG or IgA. Cultures that did produce multiple immunoglobulin isotypes occurred with a frequency predicted by the random distribution of B cells committed to production of a single isotype. A similar independent distribution of IgM anti-tetanus toxoid and IgG anti-tetanus toxoid antibody-producing precursors was observed when B cells selected on the basis of surface IgM were used in the microcultures. These results suggest that PWM-reactive B cells are at a stage of maturation in vivo such that they have the potential to secrete a single immunoglobulin isotype when activated in vitro.     

Polyclonal B cell activation in alcoholic patients with no evidence of liver dysfunction.

Unstimulated and pokeweed mitogen (PWM) stimulated immunoglobulin (Ig) synthesis by peripheral blood mononuclear cells (PBMC) in vitro and plasma Ig concentrations were measured in three groups of alcoholic patients: (i) with clinical or biochemical signs of liver disease, (ii) with evidence of an alcohol related disease but no overt signs of liver damage and (iii) with no evidence of any alcohol related disease. The concentrations of IgG and IgA were significantly raised in the supernatants of unstimulated cultures of PBMC from the patients, while the stimulation of Ig synthesis by PWM, measured as a stimulation index, was significantly reduced. The ratio of the concentration of IgG to IgA was reduced in the unstimulated cultures of PBMC from the alcoholics, indicating a greater relative increase in IgA synthesis compared to IgG synthesis. Comparing the alcoholics to the controls, it was found that the concentration of IgA in the plasma of the alcoholics was increased, but that the concentration of IgG was not altered. Comparing the different groups of patients, it was found that the concentration of IgG in the plasma was higher in the alcoholics with evidence of liver damage compared to alcoholics with alcohol related disease but no evidence of liver damage, and that the concentration of IgA in the plasma was higher in alcoholics with liver damage than those without. Otherwise there were no differences between the alcoholics with respect to the synthesis of IgG or IgA or the plasma Ig concentrations. These results indicate that IgG synthesis by PBMC in vitro, and serum Ig concentration in vivo, are abnormal in all alcoholics, not just those with overt clinical or biochemical signs of liver damage.     

An in vitro assessment of cellular and humoral immune function in pulmonary tuberculosis: correction of defective neutrophil motility by ascorbate, levamisole, metoprolol and propranolol.

Fifty-six tuberculosis patients and twenty-eight control subjects were evaluated in a comprehensive investigation of cellular and humoral immune function in pulmonary TB. The patient group showed significantly higher levels of secretory IgA and serum IgG, IgA and IgM than did the control group but 7% of patients displayed a selective secretory IgA deficiency. Levels of alpha-1-antitrypsin were also significantly higher in the patient group. There were no significant differences in levels of total haemolytic complement, C'3 and C'4. In moderate to moderately advanced TB patients there were no significant differences in T and B cell numbers nor in mitogen-induced lymphocyte transformation and lymphokine production, when compared with the control group. The range of PPD-induced lymphocyte transformation and lymphokine production levels encountered was similar in both groups although certain patients did not respond to the PPD antigen. Neutrophils from TB patients showed increased random motility in vitro but eight out of ten patients showed impaired directed motility (chemotaxis). Phagocytic and anti-microbial functions were normal in the patient group. The neutrophil chemotactic defect was reversible and could be corrected in vitro when the patients' cells were treated with sodium and calcium ascorbate, levamisole, metoprolol and propranolol.     

Analysis of IgG subclass production in cell cultures from IgA deficient patients and in normal controls as a function of age

IgA deficient individuals may also have low serum levels of IgG subclasses, especially IgG2. In the present study we examined the development of plasma cells producing IgM, IgA or IgG, and the IgG1 and IgG2 subclasses, following lipopolysaccharide (LPS) and pokeweed mitogen (PWM) stimulation of mononuclear cells (MNC) from normal and IgA deficient individuals as a function of age. Studies of blood MNC from 38 normal donors (age range 2-44 years) revealed an age-related distribution pattern of mu, gamma, alpha, gamma 1 and gamma 2 plasma cells produced in mitogen-stimulated and control cultures. Decreased IgA responses to both LPS and PWM were consistently observed in cultures of MNC from all of the nine children with IgA deficiency. When compared with age-matched controls the IgG response was also diminished in PWM stimulated cultures, whereas the IgM responses were normal. The IgG deficit was due to reduced responses for the gamma 1 and gamma 2 subclasses, and was most pronounced for IgG2; IgG2 plasma cell differentiation was particularly depressed in LPS cultures. In contrast to normal adult cells, blood MNC from the nine children with IgA deficiency and age-matched controls (2-17 years) yielded more IgG1 than IgG2 plasma cells in both control and LPS cultures, while the pattern of response to PWM was similar in all groups (gamma 1 greater than gamma 2). A good concordance was found between the level of secreted Ig in the culture supernatants and the relative number of IgM or, IgG and IgA plasma cells identified by immunofluorescence staining of cytoplasmic immunoglobulins.     

Detection and characterization of IgE-producing cells in patients with clonorchiasis

The ability of peripheral B cells of patients with Clonorchis sinensis infections to secrete IgE spontaneously was investigated in vitro. The de novo synthesis of IgE was observed in unstimulated B-cell cultures of patients. There was a significant relationship between the serum IgE level and the amount of IgE spontaneously secreted by B cells. Pretreatment of patients' B cells with 10 micrograms/ml of rabbit anti-human IgE resulted in the clear suppression of spontaneous IgE synthesis without affecting the IgG synthesis. Their B cells capable of spontaneously secreting IgE were partially sensitive to irradiation with 1,000 rad. The results obtained suggest that such IgE-forming cells may be responsible for at least part of the persistent IgE formation in patients with helminthic infections as well as in those with atopic disease.     

Immunological study of IgA deficiency during anticonvulsant therapy in epileptic patients.

Of 10 epileptic children with IgA deficiency, one showed normal IgA synthesis and secretion on in vitro pokeweed mitogen (PWM) stimulated lymphocyte culture in contrast to IgA deficiency in vivo, two showed IgA synthesis in cytoplasm without any release of IgA into the supernatant and seven failed to synthesize IgA. Co-cultures with allogeneic T or B cells in various combinations with PWM showed intrinsic IgA-B cell defect without T cell defect in two of the second group affected at IgA secretion and in five of the third group, and intrinsic IgA-B defect with dysfunction of T cells in two of the third group. Thus, the IgA deficiency in these epileptic patients was demonstrated to be heterogenous.     

Combined immunodeficiency due to the selective absence of CD4 inducer T lymphocytes

Selective congenital deficiency of the CD4 inducer T lymphocyte subset is a recently described variant of combined immunodeficiency. To further characterize the cellular and molecular mechanisms which lead to the profound T and B cell immunodeficiency in this condition, we examined in vitro immunoregulatory T lymphocyte activation and effector function, interleukin-2 (IL-2) synthesis, IL-2 receptor generation, and CD4 gene structure. Immunophenotyping of T lymphocytes demonstrated a selective deficiency of CD4+ cells, with normal numbers of CD2+ and CD3+ T cells, nearly all of which expressed the CD8+ determinant. Mitogen- and alloantigen-induced blastogenesis was profoundly decreased. B lymphocytes were present in normal numbers but there was a functional dysgammaglobulinemia (low IgG, normal IgM, low IgA) with no antibody response to in vivo immunization. T cells from the patient did not provide help to normal B cells for in vitro immunoglobulin synthesis; however, the patient's B cells were capable of synthesizing normal amounts of IgG when provided help from normal T cells. Concanavalin A failed to activate suppressor-inducer function in the patient's T cells. However, CD8+ T cell-mediated suppression was expressed if the patients T cells were cocultured with normal CD4+ T cells in a pokeweed mitogen-stimulated IgG secretion assay. IL-2 secretion and IL-2 receptor expression were both markedly reduced. Southern blot analysis of genomic DNA revealed no obvious abnormality in CD4 gene structure. The global defects in T cell activation, effector function, immunoregulation, and lymphokine generation observed in CD4+ inducer lymphocyte deficiency emphasizes the central role that the CD4 T lymphocyte plays in the activation and regulation in vivo immune responses.     

In vitro response of human peripheral blood lymphocytes of protein A. DNA synthesis and generation of cells synthesizing the three major classes of Ig.

Increased DNA synthesis and immunoglobulin secretion was observed in human peripheral blood lymphocytes (PBL) cultured in vitro with soluble protein A from Staphylococcus aureus (Sp-A). Optimal Ig secretion was obtained in 6 day cultures containing 1 x 10(6) cells/ml and 10 microgram/ml Sp-A. The presence of 5 x 10(-5) M 2-mercaptoethanol in the culture medium as well as careful selection of foetal calf serum were needed for optimal results. In response to Sp-A stimulation, the three main classes of immunoglobulins were secreted by PBL. In some individuals, concentration of Sp-A optimal for IgG and IgM secretion inhibited IgA production. Immunoglobulin-containing cells were less abundant (0.5--5% of total cells) and smaller in Sp-A than in PWM-stimulated cultures (5--15%). The data suggest that Sp-A and PWM stimulated different subsets of circulating lymphocytes.     

T-Cell Helper Activity and B-Cell Function of Synovial and Blood Lymphocytes from Patients with Rheumatoid Arthritis or Other Forms of Chronic Arthritis

The helper effect of T cells on B-cell immunoglobulin (Ig) responses induced by pokeweed mitogen (PWM) or purified protein derivative of tuberculin (PPD) was studied in lymphocytes from synovial fluid (SF) and blood of nine patients with rheumatoid arthritis (RA) and eight patients with other forms of chronic arthritis. In PWM cultures the helper effect of SF T cells on Ig responses (IgG, IgM, IgA) of autologous and allogeneic blood B cells was lower than that of blood T cells (P less than 0.01). This decrease was more pronounced in patients with RA than in patients with non-RA. In PPD cultures no significant difference was found between the helper effect of SF T cells and blood T cells on the Ig responses of allogeneic blood B cells or on the IgG response of autologous blood B cells, whereas the helper effect of SF T cells on the IgM and IgA responses of autologous blood B cells was decreased. The Ig responses to PWM or PPD in cocultures of autologous blood B and T cells were not significantly different between patients and healthy controls. The PWM- and PPD-induced Ig responses of SF B cells were lower than those of blood B cells when cocultured with autologous blood T cells. SF B cells produced IgG but usually little IgM and IgA. Thus there was a dysfunction of SF B cells and of SF T cells in a PWM-driven system, but a fairly good helper function of SF T cells in a PPD-driven system.     

Bovine IgG and human immune responses: Con A-induced mitogenesis of human mononuclear cells is suppressed by bovine IgG

Cow's milk contains 0.6-0.9 mg/ml of IgG. Under certain circumstances humans might potentially absorb significant amounts of bovine IgG and/or large fragments of bovine IgG from their diets. Normal human peripheral blood mononuclear cells were cultured with bovine milk IgG and various mitogens to begin to investigate whether bovine IgG might influence human immunologic responses. Elsewhere we have shown that bovine milk IgG at concentrations of 300 micrograms/ml completely suppressed synthesis of IgG, IgA, and IgM (96-98% suppression) in pokeweed (PWM)-stimulated cultures. Suppression was dose dependent from 40 to 300 micrograms/ml. Milk-derived bovine IgG heated at 63 degrees C during 30 min was more potent in suppression than unheated IgG. IgG from goat's milk also suppressed Ig synthesis. Bovine serum IgG and other xenogeneic serum immunoglobulins, even when heat-aggregated, had little effect on Ig synthesis. Preincubation of MNCs with bovine milk IgG and PWM for 1 day followed by washing and incubation with PWM for 14 days resulted in suppression of antibody secretion. In this study, Con A-stimulated cultures were pulsed after 3 or 4 days with 3H-thymidine for 4 h, and mitogenic responses were measured. Bovine IgG at concentrations as low as 300 micrograms/ml significantly suppressed the mitogenic response of human mononuclear cells. These studies suggest that ingested milk immunoglobulins may have the potential to modulate immune responses in humans.