Immune Deficiency of Cataract Shionogi (Cts) Mouse. H. Impaired in Vivo T Cell-Mediated Immune Response

Our previous study demonstrated that cataract Shionogi (CTS) mice, an inbred strain related to non-obese diabetic (NOD) mice, are T lymphocytopenic and that their T cell-mediated in vitro reactions, such as proliferative responses of spleen cells to T cell mitogens and alloantigens or production of IL 2 and IL 2 receptors after stimulation of spleen cells with Con A, are greatly reduced. To confirm these in vitro characteristics, in vivo immune responses of CTS mice to T-dependent and T-independent antigens were compared with those of some reference strains including NOD mice. Antibody responses of CTS mice after one injection of a high dose (10⁸) or one or two injections of a low dose (10⁵) of sheep red blood cells (SRBC) were markedly lower than those of the reference strains. The decrease was particularly striking in the IgM antibody production at primary response to both high and low doses, and the IgG antibody production at the secondary response to low dose. Similar lower antibody production was observed in CTS mice against bovine serum albumin (BSA). Little production of IgE antibody was observed from 1 through 3 weeks after an injection of BSA plus Bordetella pertussis. IgG₁ response was observed at high incidence but lower in titer than those in the reference strains. Unexpectedly, in spite of the poor antibody production to BSA, potent systemic sensitization for anaphylactic shock was easily established; incidence of lethal shock being comparable with those in the reference strains. This suggests that CTS mice are highly susceptible to the effector phase of active anaphylactic shock. Cell-mediated immunity was also impaired. Delayed type of hypersensitivity to SRBC was low, and the rejection of the skin graft from NOD mouse did not occur. In contrast to the reduced T cell-mediated responses, no difference was found between CTS and reference strains with regard to the antibody production to LPS, a T-independent antigen. These in vivo findings are consistent with the previous in vitro study.     

Immune deficiency of cataract Shionogi (CTS) mouse. II. Impaired in vivo T cell-mediated immune response

Our previous study demonstrated that cataract Shionogi (CTS) mice, an inbred strain related to non-obese diabetic (NOD) mice, are T lymphocytopenic and that their T cell-mediated in vitro reactions, such as proliferative responses of spleen cells to T cell mitogens and alloantigens or production of IL 2 and IL 2 receptors after stimulation of spleen cells with Con A, are greatly reduced. To confirm these in vitro characteristics, in vivo immune responses of CTS mice to T-dependent and T-independent antigens were compared with those of some reference strains including NOD mice. Antibody responses of CTS mice after one injection of a high dose (10(8)) or one or two injections of a low dose (10(5)) of sheep red blood cells (SRBC) were markedly lower than those of the reference strains. The decrease was particularly striking in the IgM antibody production at primary response to both high and low doses, and the IgG antibody production at the secondary response to low dose. Similar lower antibody production was observed in CTS mice against bovine serum albumin (BSA). Little production of IgE antibody was observed from 1 through 3 weeks after an injection of BSA plus Bordetella pertussis. IgG1 response was observed at high incidence but lower in titer than those in the reference strains. Unexpectedly, in spite of the poor antibody production to BSA, potent systemic sensitization for anaphylactic shock was easily established; incidence of lethal shock being comparable with those in the reference strains. This suggests that CTS mice are highly susceptible to the effector phase of active anaphylactic shock. Cell-mediated immunity was also impaired. Delayed type of hypersensitivity to SRBC was low, and the rejection of the skin graft from NOD mouse did not occur. In contrast to the reduced T cell-mediated responses, no difference was found between CTS and reference strains with regard to the antibody production to LPS, a T-independent antigen. These in vivo findings are consistent with the previous in vitro study.     

Genetic Control of the Murine Cell-Mediated Immune Response In Vivo

Various inbred and congenic strains of mice were immunized with the linear terpolymer L-glutamic acid⁶⁰-L-alanine³⁰-L-tyrosine¹⁰ (GAT). Using a radioisotopic footpad assay to measure cell-mediated immunity in vivo, mice with H-2^a, H-2^b, H-2^d, and H-2^k histocompatibility alleles showed a positive reaction, whereas mice with H-2^P and H-2^S alleles failed to respond. The ability of 'responder'. lymphocytes to show an immune response resides in the thymus-derived (T) lymphocyte population. Unfractionated spleen cells from H-2^q nonresponder mice, on transfer, showed no reactivity, whereas T-cell-enriched preparations were active.     

Genetic Basis of Memory in Cell-Mediated Immune Response

The present experiments were undertaken to delineate the role of LD and SD antigens in terms of memory in cell-mediated immune response (CML). Using recombinants that differ for either the H-2K or H-2D determinants (SD-different) and other recombinants differing for the central region of H-2 (LD-different), we have investigated this question. The results indicate that priming to SD determinants leads to a more rapid and higher response when cells are restimulated in vitro with either the same SD antigen alone or the same SD plus an LD antigen and tested on target cells that possess either the SD antigen alone or both the LD and SD antigen. Antigens in the central regions of H-2, which includes LD, serve as the stimulus both for the helper T cells and for the cytotoxic T lymphocytes. Priming with a high dose of LD antigens leads to memory in the cytotoxic T lymphocyte recognizing the cytotoxic target antigens coded by the central region of H-2. Nevertheless, memory could not be detected when priming was done under the same conditions as for SD antigens. Moreover, a primed helper T-cell response does not facilitate the development of increased CML on restimulation in vitro with the LD antigen used for priming and a new SD antigen. Thus, it seems that memory in CML is in the cytotoxic T lymphocyte and not in the proliferating helper cells.     

Cell-Mediated Immune Response in Cattle to Mycoplasma mycoides var. mycoides

The cell-mediated immune response of cattle to Mycoplasma mycoides var. mycoides was studied. Sensitized lymphocytes in blood leukocyte preparations showed a significant degree of antigen-induced transformation, judged by the uptake of tritiated thymidine. The increase in tritiated thymidine uptake in sensitized lymphocytes in the presence of M. mycoides membrane antigen varied from 2- to 13-fold compared with the controls, and this increase in activity was observed from 3 days after artificial infection. Inhibition of leukocyte migration by M. mycoides membrane antigen commenced between 17 and 30 days after infection, and preliminary observations indicate that this test correlated with the intradermal allergic test. M. mycoides-induced unresponsiveness was demonstrated 23 and 30 days after infection. Unresponsiveness, in that the lymphocytes did not respond to phytohemagglutinin, was very marked in two of three animals and partial in the third animal, whereas the humoral antibody response did not appear to be affected. Antigen-induced transformation was demonstrated in only two out of six cattle vaccinated two months previously with M. mycoides T₁ broth culture vaccine, and óne animal only gave a doubtful intradermal allergic reaction. A further six cattle vaccinated 15 months previously were negative to both the leukocyte migration inhibition test and the intradermal allergic test.     

Effect of Macrophage Colony-Stimulating Factor (M-CSF) on Mouse Immune Responses in Vivo

We examined the effects of recombinant human M-CSF (rhM-CSF) on mouse macrophages and immune responses in vivo. Intraperitoneal administration of rhM-CSF (20-500 μg/ml) increased Mac-l⁺ cell numbers in the peritoneal cavity. The tumoricidal activities of the macrophages from vehicle-administered (V-MΦ) and from rhM-CSF-administered (M-MΦ) mice were the same as those observed in vitro. However, when activated by lipopolysaccharide (LPS), the tumoricidal activity of M-MΦ was stronger than that of V-MΦ. Intravenous administration of rhM-CSF (500 μ g/gk) increased the number of spleen cells. Flow cytometric analysis showed that administration of rhM-CSF increased Mac-1⁺, B220+ and NK 1.1⁺ cell counts in the spleen. However, CD4⁺ and CD8⁺ cell numbers did not change. Concomitant increases were observed in levels of IL-4 and IL-10 in mouse serum following rhM-CSF administration, but no significant changes were observed in the serum level of IFN-γ.

In experiments involving mouse immune responses, the administration of rhM-CSF reduced the contact sensitivity (CS) reaction against picryl chloride (PC) and augmented IgE production in response to 2,4-dinitrophenyl (DNP), but did not affect the production of either IgM or IgG 1.

These results suggest that administration of rhM-CSF not only activates murine macrophages, but modulates antigen-specific immune responses in vivo.     

Effect of Biophytum sensitivum on Cell-Mediated Immune Response in Mice

Effect of Biophytum sensitivum on cell-mediated immune response was studied in normal as well as Ehrlich ascites tumor bearing BALB/c mice. Administration of Biophytum sensitivum significantly enhanced the proliferation of splenocytes, thymocytes and bone marrow cells by stimulating the mitogenic potential of various mitogens such as Lipopolysaccharide (LPS), Concanavalin A (Con A), Phytohaemagglutinin (PHA) and Poke Weed Mitogen (PWM). Natural killer (NK) cell activity was enhanced significantly by Biophytum sensitivum in both the normal (43.6% cell lysis on day 5) and the tumor bearing group (48.2% cell lysis on day 5), and it was found to be earlier than tumor bearing control animals (maximum of 13.4% cell lysis on day 9). Antibody dependent cellular cytotoxicity (ADCC) was also enhanced significantly in both Biophytum treated normal (35% cell lysis on day 7) as well as tumor bearing animals (40.2% cell lysis on day 7) compared to untreated control tumor bearing animals (maximum of 12.3% cell lysis on day 11). An early antibody dependent complement mediated cytotoxicity (ACC) was also observed in the Biophytum treated normal (22.6% cell lysis, on day 15) and tumor bearing animals (26.4% cell lysis, on day 15). Results of our present study suggest the immunomodulatory property of Biophytum sensitivum.     

Effect of Biophytum sensitivum on Cell-Mediated Immune Response in Mice

Effect of Biophytum sensitivum on cell-mediated immune response was studied in normal as well as Ehrlich ascites tumor bearing BALB/c mice. Administration of Biophytum sensitivum significantly enhanced the proliferation of splenocytes, thymocytes and bone marrow cells by stimulating the mitogenic potential of various mitogens such as Lipopolysaccharide (LPS), Concanavalin A (Con A), Phytohaemagglutinin (PHA) and Poke Weed Mitogen (PWM). Natural killer (NK) cell activity was enhanced significantly by Biophytum sensitivum in both the normal (43.6% cell lysis on day 5) and the tumor bearing group (48.2% cell lysis on day 5), and it was found to be earlier than tumor bearing control animals (maximum of 13.4% cell lysis on day 9). Antibody dependent cellular cytotoxicity (ADCC) was also enhanced significantly in both Biophytum treated normal (35% cell lysis on day 7) as well as tumor bearing animals (40.2% cell lysis on day 7) compared to untreated control tumor bearing animals (maximum of 12.3% cell lysis on day 11). An early antibody dependent complement mediated cytotoxicity (ACC) was also observed in the Biophytum treated normal (22.6% cell lysis, on day 15) and tumor bearing animals (26.4% cell lysis, on day 15). Results of our present study suggest the immunomodulatory property of Biophytum sensitivum.     

Effects of Carbon Dust Inhalation on the Cell-Mediated Immune Response in Mice

The effects of carbon dust inhalation on the bone marrow-derived (B) and thymus-derived (T) lymphocyte populations of spleen and mediastinal lymph node (MLN) cultures were examined. The concanavalin A (Con A)-responsive cell population (T cells) in the spleen was found to be depressed after 7 days of pre-exposure to carbon dust. However, this effect was transient, and after 14, 21, and 28 days of pre-exposure to carbon dust, the Con A-responsive cells exhibited a 30 to 40% enhancement over control group responses. Conversely, Con A-responsive cells in the pooled MLN cultures exhibited depression, ranging from 22 to 33% below control group values, after 7, 14, and 28 days of pre-exposure to carbon dust. The lipopolysaccharide (LPS)-responsive cell population (B cells) in the spleens of carbon-exposed mice was found not to differ significantly from control group values after all times of pre-exposure. LPS-responsive cells in the MLN cultures exhibited enhancement, ranging from 49 to 74% above control values, after 14, 21, and 28 days of pre-exposure to carbon dust. The ability of carbon spleen cell cultures from carbon-exposed mice to undergo antigen induced blast transformation after sensitization with Mycobacterium tuberculosis H37Ra was also determined. Mice exposed to carbon dust inhalation 2 weeks before and 3 weeks after aerosol or subcutaneous immunization exhibited significantly enhanced ratios of transformation upon culture of their spleen lymphocytes with purified protein derivative of tuberculin.     

Control of the Immune Response: Role of Macrophages in Regulation of Antibody-and Cell-Mediated Immune Responses

The ability of peritoneal macrophage subpopulations, separated into different classes according to their size, to reconstitute antibody or cellular immune responses in macrophage-depleted spleen cells has been investigated. Data are presented to show that whether reconstitution is by 'normal' or 'activated' macrophages, be they syngeneic or allogeneic to the lymphocyte source, different populations reconstitute antibody and cellular immunity. Reconstitution is in general by two classes of macrophages, small and large. The former seem to reconstitute only if syngeneic to the responding lymphocyte pool, whereas large macrophages reconstitute immune responses from allogeneic lymphocytes as well as syngeneic lymphocytes. Evidence is also presented to show that syngeneic large macrophages can determine the type of immune response reconstituted; that is, with greater numbers of large cells only cytotoxic responses (and not T-dependent antibody formation) were reconstituted and vice versa.     

Influence of Arecoline on Immune System: III. Suppression of B Cell-Mediated Immune Response in Mice After Short-Term Exposure

Abstract

Arecoline, a major alkaloid of arecanut was examined to explore its modulatory influence on B cell-mediated immune response in a murine model system. The in vivo and in vitro effects were evaluated at sub-toxic concentrations of arecoline. The number of primary antibody forming cells (AFC) and hemagglutinating and hemolysis antibody titers to Sheep Red Blood Cells (SRBC) were evaluated in male mice. Arecoline exposure for a week invoked dose-dependent effect on primary antibody forming cells to SRBC with a maximum reduction at the dosage of 20 mg/kg bw, a moderate reduction at 10 mg/kg bw and no effect at 5 mg/kg bw dose level. HA and HL antibody titers to SRBC were suppressed markedly at arecoline dosage of 20 mg/kg bw and moderately at a dose of 10 mg/kg bw, given daily for 1, 2 or 3 weeks. The inhibitory effect of arecoline was not dependent on the duration of treatment. Like the primary antibody response, the secondary HA and HL antibody titers were also decreased after arecoline exposure. The administration of arecoline dosages 10 and 20 mg/kg bw daily for 4 days following SRBC immunization also, exerted dose-dependent suppression of primary antibody response. Similarly, when treated after 12 h following immunization, significant reduction in response was observed with arecoline dosage of 20 mg/kg bw. While moderate suppression of antibody response was noticed at the dose level of 10 mg/kg bw, there was no alteration in response at a dosage of 5 mg/kg bw. In contrast, arecoline dosages 5, 10 or 20 mg/kg bw given after 1, 2 or 4 days following immunization did not alter the HA and HL antibody titers to SRBC. Recovery experiments in mice revealed that arecoline-mediated suppression of antibody response is of a reversible nature. Concomitant exposure of arecoline at the concentrations of 10^?5 – 10^?4 M with PWM suppressed ³H-thymidine incorporation of splenic cells in vitro. Taken together, the findings reported in this paper suggest that the intensity of arecoline-mediated suppression of antibody response to SRBC and PWM-induced splenic cell proliferation is dependent upon the dosage and the mode of treatment.     

Chronic Active Hepatitis Induced by Helicobacter hepaticus in the A/JCr Mouse Is Associated with a Th1 Cell-Mediated Immune Response

Helicobacter hepaticus infection in A/JCr mice results in chronic active hepatitis characterized by perivascular, periportal, and parenchymal infiltrates of mononuclear and polymorphonuclear cells. This study examined the development of hepatitis and the immune response of A/JCr mice to H. hepaticus infection. The humoral and cell-mediated T helper immune response was profiled by measuring the postinfection (p.i.) antibody response in serum, feces, and bile and by the production of cytokines and proliferative responses by splenic mononuclear cells to H. hepaticus antigens. Secretory immunoglobulin A (IgA) and systemic IgG2a antibody developed by 4 weeks p.i. and persisted through 12 months. Splenocytes from infected mice proliferated and produced more gamma interferon (IFN-γ) than interleukin-4 (IL-4) or IL-5 when cultured with H. hepaticus outer membrane proteins. The predominantly IgG2a antibody response in serum and the in vitro production of IFN-γ in excess of IL-4 or IL-5 are consistent with a Th1 immune response reported in humans and mice infected with Helicobacter pylori and Helicobacter felis, respectively. Mice infected with H. hepaticus developed progressively severe perivascular, periportal, and hepatic parenchymal lesions consisting of lymphohistiocytic and plasmacytic cellular infiltrates. In addition, transmural typhlitis was observed at 12 months p.i. The characterization of a cell-mediated Th1 immune response to H. hepaticus infection in the A/JCr mouse should prove valuable as a model for experimental regimens which manipulate the host response to Helicobacter.     

Inhibition of Tumor Growth and Metastases in Mice Bearing a Malignant Fibrosarcoma by T Cell-Mediated Immune Response to Oncofetal Antigens

ABSTRACT: The presence of fetal antigens on a wide variety of tumors has been well-documented it has been attributed, for the most part, to de-repression of genes normally operative in the early stages of embryonic development. Controversy still exists, however, about the role of fetal antigens in antitumor immunity. It is not clear whether the tumor inhibition shown in some systems is due to an immune response. In the present study, conducted in a weakly immunogenic Lewis T241 fibrosarcoma, syngeneic for C57B1/ 6J mice, immunization of normal mice with syneneic fetal cells resulted in striking inhibition of growth and metastases of tumors. On the other hand, immunization with syngeneic normal, adult spleen cells or with allogeneic A/J fetal cells did not inhibit tumor growth or metastases. Mice that had gone through single pregnancy also showed inhibition in tumor growth and metastases. Immunization of female mice with syngeneic tumor cells or fetal cells, prior to pregnancy, resulted in a high incidence of fetal death in these mice. Further studies showed that tumor inhibitory response evoked by fetal cell immunization was due to fetal antigens the male-specific HY antigen was not responsible for antitumor response. When tumor cells were mixed with spleen cells from fetal antigen-immunized mice and then injected into normal mice (Winn neutralization assay), significant inhibition of tumor growth and metastases was observed. In this assay, mixing tumor cells with syngeneic fetal cells, normal adult spleen cells, or spleen cells from C57 mice immunized with allogeneic fetal cells did not inhibit the tumor growth or metastases. These results show that inhibition in tumor growth and metastases, following fetal cell immunization, was due to a specific immune response to the oncofetal antigens involved. Analysis of effector cells showed them to be T cells of Lyt-1⁺ and Lyt-2^? phenotype.     

Cell-Mediated Immune Response in the Mammary Gland of Guinea Pigs Adoptively Sensitized With Lymphocytes

ABSTRACT: Guinea pigs were vaccinated intramammarly (IMM) with attenuated Mycobacterium bovis (BCG) and challenged intramammarly and intradermally with tuberculin. A significant (p < 0.05) milk leukocytosis, consisting primarily of polymorphonuclear leukocytes, occurred from 6–30 hr after challenge with tuberculin. Intradermal challenge with tuberculin produced typical delayed-type hypersensitivity cutaneous reaction in these animals. Normal guinea pigs were adoptively sensitized with lymphoid cells from the inguinal lymph nodes or spleen of BCG-vaccinated animals and subsequently challenged intramammarly and intradermally with tuberculin. The mammary and dermal responses of the lymphoid cell recipients were similar to, but less pronounced, than those in the actively immunized animals. The responses in the recipients of lymphocytes from donors injected with tuberculin 18 hr prior to cell collection were greater than those from injected donors. Guinea pigs that were injected intraperitoneally with serum from BCG-vaccinated donors did not express significant dermal or mammary responses to subsequent challenge with tuberculin. It was proposed that the milk leukocytosis was mediated by sensitized lymphocytes stimulated by IMM challenge with tuberculin.     

Mouse Strain-Dependent Chemokine Regulation of the Genital Tract T Helper Cell Type 1 Immune Response

Vaginal infection with the mouse pneumonitis agent of Chlamydia trachomatis (MoPn) produces shorter courses of infection in C57BL/6 and BALB/c mice than in C3H/HeN mice, while C57BL/6 mice are more resistant to oviduct pathology. A robust Th1 response is extremely important in host defense against chlamydia. In this study we examined gamma interferon (IFN-gamma), interleukin 10 (IL-10), and the T-cell-regulatory chemokines macrophage inflammatory protein-1alpha (MIP-1alpha) and monocyte chemoattractant protein-1 (MCP-1) to determine if differences in these responses were associated with the differential courses of infection seen in these three strains of mice. Increased and prolonged IFN-gamma responses and lower IL-10 responses were observed in the C57BL/6 strain compared to BALB/c and C3H. Examination of genital tract chemokines revealed a marked predominance of MIP-1alpha over MCP-1 only in the C57 strain. Thus, a pattern of high MIP-1alpha and low MCP-1 levels during the first week of infection is associated with an increased Th1 response and a shorter, more benign chlamydial infection. Inhibition of the MCP-1 response in C3H mice increased their later T-cell production of IFN-gamma but decreased their early IFN-gamma response and had no effect on the course or outcome of infection. Inhibition of MCP-1 is not beneficial in chlamydial infection because of its pleiotropic effects.     

Suppression of Humoral and Cell-Mediated Immune Responses in Vitro by Benzo (A) Pyrene

The effect of benzo(a)pyrene (BaP) at different molar (MI concentrations on the in vitro anti-sheep red blood cell (SRBC) plaque (antibody) forming cell (PFCI response and the one-way mixed lymphocyte response (MLR) was tested. Inhibition of the PFC response and the MLR occurred when spleen cells were exposed to a wide range of BaP concentrations from 10^-4 m to 10^-8 m. Maximum depression of the responses occurred at 10^-5 M for PFC production (47% of controls) and for the MLR (19% of controls) as measured by a stimulation index. No significant loss in cell viability was observed at this or lower molar concentrations of BaP. The non-carcinogenic analog of BaP, benzo(e)pyrene, did not suppress PFC responses at comparable concentrations. This in vitro system will facilitate manipulations of T and B lymphocytes and macrophages (adherent cells) in a controlled culture environment for precisely characterizing the sensitivity of these cells and their subpopu-lations on exposure to BaP.     

Suppression of Humoral and Cell-Mediated Immune Responses in Vitro by Benzo (A) Pyrene

Abstract

The effect of benzo(a)pyrene (BaP) at different molar (MI concentrations on the in vitro anti-sheep red blood cell (SRBC) plaque (antibody) forming cell (PFCI response and the one-way mixed lymphocyte response (MLR) was tested. Inhibition of the PFC response and the MLR occurred when spleen cells were exposed to a wide range of BaP concentrations from 10^–4 m to 10^–8 m. Maximum depression of the responses occurred at 10^–5 M for PFC production (47% of controls) and for the MLR (19% of controls) as measured by a stimulation index. No significant loss in cell viability was observed at this or lower molar concentrations of BaP. The non-carcinogenic analog of BaP, benzo(e)pyrene, did not suppress PFC responses at comparable concentrations. This in vitro system will facilitate manipulations of T and B lymphocytes and macrophages (adherent cells) in a controlled culture environment for precisely characterizing the sensitivity of these cells and their subpopu-lations on exposure to BaP.     

Assessment of Markers of the Cell-Mediated Immune Response after Influenza Virus Infection in Frail Older Adults

The purpose of this study was to determine whether measures of the cell-mediated immune response to influenza virus could be used as markers of influenza virus infection. We studied 23 subjects who developed upper respiratory, lower respiratory, or systemic symptoms during a small outbreak of influenza in a nursing home population. Influenza virus culture from nasopharyngeal swabs yielded influenza virus isolates from 7 of the 23 subjects. Only three of the subjects had a fourfold rise in antibody titer to the influenza virus antigen positivity after the infection. Granzyme B and cytokine levels were measured in peripheral blood mononuclear cells (PBMC) obtained from all subjects and stimulated with live influenza virus. Elevated granzyme B levels in virus-stimulated PBMC in combination with lower respiratory tract or systemic symptoms in study subjects was a significant predictor of culture-confirmed influenza virus infection compared to those from whom influenza virus could not be identified. Cytokine levels did not distinguish between the two groups in a similar type of analysis. Granzyme B in combination with the clinical profile of symptoms may be a useful retrospective marker for influenza virus infection.     

Impaired dendritic cell maturation and increased T(H)2 responses in PIR-B(-/-) mice

Mice deficient for paired immunoglobulin (Ig)-like receptor B (PIR-B) show defective regulation of receptor-mediated activation in antigen-presenting cells. Older PIR-B(-/-) mice had an increased number of peritoneal B1 cells. Splenic PIR-B(-/-) B2 cells were constitutively activated and proliferated much more than those from wild-type mice upon B cell receptor ligation. T helper type 2 (T(H)2)-prone humoral responses were augmented in PIR-B(-/-) mice upon immunization with T-dependent antigens, including increased interleukin 4 and decreased interferon-gamma responses, as well as enhanced IgG1 and IgE production. Impaired maturation of dendritic cells (DCs), possibly due to perturbed intracellular signaling, was responsible for the skewed responses. Thus, PIR-B is critical for B cell suppression, DC maturation and for balancing T(H)1 and T(H)2 immune responses.