IgG anti-tetanus toxoid antibody production induced by Epstein-Barr virus from B cells of human marrow transplant recipients

This investigation shows that Epstein-Barr virus (EBV)-activated human B cells from marrow transplant recipients can produce in vitro IgG anti-tetanus toxoid antibody (anti-TT) without booster immunizations with tetanus toxoid (TT). Purified B cells (E-rosette negative) from 8 normal subjects, 6 healthy long-term marrow graft recipients, and 15 long-term marrow graft recipients with chronic graft-vs-host disease (GVHD), were stimulated for 12 days with EBV to induce anti-TT production in culture supernatants. The amount of anti-TT in culture supernatants was quantitated using a enzyme-linked immunosorbent assay. B cells from all 8 normal controls produced in vitro IgG anti-TT after EBV stimulation. Five of 6 healthy recipients had B cells that produced anti-TT after EBV stimulation. Four of 15 recipients with chronic GVHD had B cells capable of producing anti-TT after EBV stimulation. The number of cultures making anti-TT responses was less in those with chronic GVHD than in those without chronic GVHD or normal individuals (P less than 0.001). B cells from patients with chronic GVHD had fewer responses exceeding the overall median of 0.7 ng/ml when compared with the other two groups (P less than 0.03). These data show that B cells of donor origin can produce in vitro IgG anti-TT antibody to tetanus toxoid antigen in a T-independent fashion.     

Mucosal and systemic immune responses of mice to tetanus toxoid coadministered nasally with AFCo1

Mucosal immune responses are an early and important line of defense against pathogens. The current understanding of the mucosal immune system allows us to consider the use of nasal immunization for induction of antigen-specific immune responses at the mucosal surface and the systemic compartment. Mucosal adjuvants are key for developing novel mucosal vaccines and represent 1 approach to improving mucosal and systemic immunity. However, few mucosal vaccine adjuvants are currently approved for human use. Neisseria meningitidis B proteoliposome-derived cochleate (AFCo1 - Adjuvant Finlay Cochleate 1) has been demonstrated to be a potent mucosal adjuvant. The present work demonstrates that intranasal immunization of 3 doses of tetanus toxoid (TT) coadministered with AFCo1 in mice promotes high systemic and mucosal responses. The anti-TT IgG serum titers and the mucosal anti-TT IgA in saliva and vaginal wash were significantly higher than TT alone. The analysis of antibody subclasses showed that intranasal administration of AFCo1 + TT induced not only IgG1 but also IgG2a anti-TT antibodies at levels comparable to those obtained with TT vaccine (vax-TET). These data support the fact that AFCo1 is a potent mucosal adjuvant in nasal immunization to a coadministered protein antigen.     

Idiotypic determinants on human T cells and modulation of human T cell responses by anti-idiotypic antibodies

The role of idiotypic anti-idiotypic interactions in the regulation of the human T cell response to tetanus toxoid (TT) antigen was examined in three subjects. Rabbit anti-idiotypic (anti-Id) antisera were raised against IgG (Fab')2 anti-TT obtained 7 to 10 days after booster immunization with TT. F(ab')2 fragments of rabbit-anti-Id IgG were used in conjunction with fluorescein-conjugated goat anti-rabbit Ig in an indirect immunofluorescence assay to determine the frequency of Id-positive cells in T cell-enriched preparations. This frequency was 24, 29, and 38 per 10,000, respectively, in the three subjects studied. Significant contribution of contaminating B cell to fluorescence-staining was ruled out by capping experiments using goat anti-human Ig (GAHIG) and by double staining experiments using rhodamine-conjugated GAHIG. Absorption of anti-Id antisera with Epstein Barr virus (EBV)-transformed B cell lines from the IgG (Fab')2 anti-TT donor, but not with EBV-B cell lines from unrelated donors, removed their reactivity with the T cells. Rabbit anti-Id IgG caused minimal proliferation (two-threefold) of T cells and had no effect on T cell proliferation in response to TT antigen when added to the cultures. Preincubation of T cells for 48 hr with rabbit anti-Id IgG (Fab')2, but not with preimmune rabbit IgG (Fab')2, resulted in the generation of antigen-specific suppressor cells that inhibited T cell proliferation in response to TT, but not in response to diphtheria toxoid (DT). These cells also inhibited the synthesis of IgG anti-TT in response to in vitro stimulation with TT antigen, but not the synthesis of IgG anti-DT in response to DT antigen. Adsorption of T cells over plates coated with rabbit anti-Id IgG (Fab')2 enhanced the proliferative response of the T cells to TT, but not to DT antigen, and enhanced the helper activity of the T cells for the in vitro synthesis of IgG anti-TT but not of IgG anti-DT antibodies. These results suggest that idiotypic-anti-idiotypic interactions play a role in the human T cell response to antigen.     

C群奈瑟氏脑膜炎球菌荚膜多糖-TT结合疫苗的制备及其在小鼠体内免疫原性的研究

将C群脑膜炎球菌荚膜多糖以ADH作为间隔剂与TT结合形成GCMP-TT结合疫苗,然后用此结合疫苗免疫NIH小鼠,结果显示使用GCMP免疫小鼠后仅能产生较低水平抗GCMP的IgG抗体,而用GCMP-TT免疫后小鼠血清中产生了较GCMP免疫显著增高抗GCMP的IgG抗体,并且GCMP-TT组第二次和第三次免疫后与初次免疫相比,IgG抗体水平均有显著升高(P<0.01),表明GCMP-TT结合疫苗具有免疫记忆和再次免疫加强应答效应。补体介导的血清抗体体外杀菌试验结果证明,GCMP-TT结合疫苗组免疫小鼠诱导的抗体IgG比GCMP组具有增强的体外杀菌活性。     

Antibodies to acetylcholine receptor and tetanus toxoid: in vitro synthesis by thymic lymphocytes

Thymic lymphocytes (TL) of patients with myasthenia gravis (MG) have been reported to synthesize antibodies to acetylcholine receptors (anti-AChR). Incubation of TL with pokeweed mitogen (PWM), a polyclonal T cell- and monocyte-dependent activator of B cell differentiation, was reported to inhibit TL in vitro synthesis of anti-AChR. We studied the TL of 16 patients with MG without thymoma. TL of 10 of 16 patients synthesized anti-AChR in vitro without stimulation. In the presence of PWM, the amount of anti-AChR synthesized by the TL of these 10 patients increased in five, decreased in three, and was unaffected in two. There was a correlation between serum anti-AChR titer and PWM-stimulated synthesis (r = 0.87), but not with unstimulated synthesis (r = 0.33) of anti-AChR by TL. There was no correlation between the amount of synthesized anti-AChR and the amount of secreted IgG or with the percentage of B cells (surface Ig+) in the TL suspensions. TL of three age-matched cardiac surgery controls failed to synthesize detectable anti-AChR, although two of three synthesized IgG. Four patients with MG were booster immunized with tetanus toxoid (TT) 3 to 4 wk prior to thymectomy. TL of three synthesized anti-TT in vitro, whereas TL of three nonboosted MG patients failed to synthesize anti-TT. Thus, we have shown that TL of some patients with MG are capable of anti-AChR synthesis, with evidence of heterogeneity of the in vitro response, and the B cell repertoire in the thymus may, in part, reflect recent systemic immune events of the host.     

Immunological memory to tetanus toxoid is established and maintained in the vitamin A-depleted rat

We have previously shown that vitamin A deficiency severely impairs the young rat's ability to produce specific antibodies after primary immunization with tetanus toxoid (TT). In the present studies, we asked whether immunologic memory to TT is established even in the vitamin A-depleted animal, and if so, whether such memory can be elicited after subsequent repletion with retinol. Vitamin A-depleted rats produced very low concentrations of TT-specific IgM and IgG antibodies in both the primary and secondary responses; however, the ratios of secondary to primary IgM anti-TT and of IgG anti-TT were normal. When rats were repleted with retinol 1 day after immunization, IgM and IgG anti-TT concentrations in both the primary and secondary responses were at least as great as those of control rats. For rats repleted with retinol 2 days before the booster immunization, secondary IgM and IgG anti-TT concentrations were equal in magnitude to those of vitamin A-sufficient controls. For all groups, the kinetics of the antibody response were similar. We conclude that immunological memory is intact in the vitamin A-depleted animal, as shown by 1) the normal ratio of its secondary to primary antibody responses, 2) the restoration of a quantitatively normal secondary antibody response in previously vitamin A-depleted animals repleted with retinol just before boosting with TT, and 3) a normal class switch from IgM to IgG. Retinol deficiency is also characterized by an abnormal elevation of total plasma IgG, despite the inability of the vitamin A-depleted animal to produce normal quantities of specific antibodies after challenge with antigen.     

Analysis of the antigen- and mitogen-induced differentiation of B lymphocytes from asymptomatic human immunodeficiency virus-seropositive male homosexuals. Discrepancy between T cell-dependent and T cell-independent activation

Five asymptomatic human immunodeficiency virus (HIV)-seropositive male homosexuals were immunized with the recall antigens tetanus toxoid (TT) and the three types of poliovirus present in diphtheria, tetanus, and polio vaccine. Four weeks after immunization, the in vivo response to booster immunization, the in vitro pokeweed mitogen (PWM)-induced IgG secretion, and the in vitro T cell-dependent and T cell-independent antigen-induced antibody response were assayed. Increase in serum antibody titer to TT and poliovirus was low and normal, respectively. In all five subjects studied, a high rate of spontaneous IgG production, including antibodies directed toward HIV was observed. Addition of PWM to the cultures induced suppression of the spontaneous IgG secretion. Only one donor showed a slightly increased IgG production after stimulation with PWM. Peripheral blood mononuclear cells of four of the five HIV-seropositive individuals did not produce TT, or poliovirus-specific antibodies when stimulated with the respective T cell-dependent antigens. However, stimulation of these peripheral blood mononuclear cells with TT coupled to agarose beads, which was shown to be T cell-independent, resulted in the generation of IgG anti-TT antibody-forming cells.     

In vitro human antibody production to the Haemophilus influenzae type b capsular polysaccharide

In vitro production of human antibody to the Haemophilus influenzae type b capsular polysaccharide (PRP) and to tetanus toxoid (TT) and diphtheria toxoid was measured in culture supernatants of peripheral blood mononuclear cells and by enumeration of antibody secreting cells (AbSC) in an enzyme-linked immunosorbent-plaquing assay. Normal adult peripheral blood mononuclear cells stimulated with Epstein-Barr virus secreted anti-PRP antibody with a frequency of 1/552 to 1/1190 relative to total Ig secreting cells; the frequency of AbSC to tetanus toxoid (TT) was 7.5 times higher (p less than 0.05). These frequencies did not change significantly after in vivo immunization, although the isotype distribution shifted toward increased IgG for TT and increased IgG and IgA for PRP. At 8 days postimmunization, spontaneous AbSC to PRP and TT were detected; frequencies for total anti-TT AbSC again being higher than anti-PRP, but there were significantly more IgA plaques among anti-PRP AbSC. Spontaneous AbSC were suppressed in culture by pokeweed mitogen and enhanced by cyclosporine. Three wk after in vivo immunization with PRP and TT, in vitro stimulation with pokeweed mitogen, Staphylococcus aureus Cowan 1 bacteria, or antigen induced anti-TT but not anti-PRP in vitro antibody secretion, although Epstein-Barr virus induced both. These data suggest that PRP, a polysaccharide, and TT, a protein, differ in their requirements for in vitro activation with antigen and mitogens.     

Assessing immune competence in pigs by immunization with tetanus toxoid

Immune competence can be tested by challenging organisms with a set of infectious agents. However, disease control requirements impose restrictions on the infliction of infections upon domestic pigs. Alternatively, vaccinations induce detectable immune responses that reflect immune competence. Here, we tested this approach with tetanus toxoid (TT) in young domestic pigs. To optimize the vaccination protocol, we immunized the pigs with a commercial TT vaccine at the age of 21 or 35 days. Booster immunizations were performed either 14 or 21 days later. TT-specific antibodies in plasma as well as lymphoproliferative responses were determined both 7 and 14 days after booster immunization using ELISA and lymphocyte transformation tests, respectively. In addition, general IgG and IgM plasma concentrations and mitogen-induced proliferation were measured. The highest TT-specific antibody responses were detected when blood samples were collected 1 week after a booster immunization conducted 21 days after primary immunization. The pigs’ age at primary immunization did not have a significant influence on TT-specific antibody responses. Similarly, the TT-specific proliferative responses were highest when blood samples were collected 1 week after booster immunization, while age and time of primary and booster immunization were irrelevant in our setup. While general IgG and IgM plasma levels were highly age dependent, there were no significant age effects for TT-specific immune responses. In addition, mitogen-induced proliferation was independent of immunization as well as blood sampling protocols. In summary, our model of TT vaccination provides an interesting approach for the assessment of immune competence in young pigs. The detected vaccination effects were not biased by age, even though our data were acquired from immune systems that were under development during our tests.     

Adjuvant properties of bacterial product cantastim

Aluminum compounds have been used as adjuvants in practical vaccination for more than 60 years to induce an early, an efficient and a long lasting protective immunity. Nowadays they are the most widely used adjuvants in both veterinary and human vaccines. Unfortunately these adjuvants do not only cause undesirable side effects, but often induce T-helper type 2 (Th2)-biased responses. In this study we investigated the ability of the bacterial product CANTASTIM (CS) to augment the immune responses to a model antigen, tetanus toxoid (TT). Immunization of mice with TT+CS elicited higher anti-TT IgG antibody levels as compared to mice that received TT alone. Moreover, treatment with TT+CS resulted in a lower IgG1/IgG2a ratio and a stronger in vitro IFN-gamma synthesis by splenocytes and T cells cocultured with macrophages. These data suggest that CS can be used to enhance the magnitude of the immune response and to skew it towards the Th1 type.     

The relationship between immunization and circulating antigen-specific plaque-forming cells

The relationship between the appearance of cells producing antibody to tetanus toxoid (TT) in the circulation and the serum titers of anti-TT IgG following booster immunization has been studied. It was found that cells producing anti-TT antibody can be detected in the circulation in a hemolytic plaque assay using sheep red blood cells (SRBC) coated with TT by the chromic chloride method. In symmetric inhibition studies using cells from TT or keyhole limpet hemocyanin (KLH)-immune donors, the homologous antigen inhibited 100% of the PFC with no cross-inhibition. Thus, the plaque-forming cells (PFC) detected in this assay are specific for the immunizing antigen. No evidence of polyclonal B-cell activation in response to TT was found, as shown by a failure to detect any PFC against unmodified or KLH or human serum albumin-treated SRBC. In addition, the increase in total Ig-secreting cells observed in a staphylococcal protein A reverse hemolytic plaque assay was always accounted for by the number of anti-TT antibody-producing cells observed. The peak number of anti-TT antibody-producing cells varied between donors, but the kinetics of their appearance was highly reproducible--none before Day 5, peak numbers between Days 6 and 8, and a sharp decline with only rare anti-TT Ig-secreting cells in the circulation by Day 15 postimmunization. Anti-TT antibody-producing cells appeared in the circulation prior to any detectable increase in serum anti-TT antibody titers, and following the disappearance of PFC from the circulation, there was no further increase in serum IgG anti-TT levels. These observations demonstrate a marked specificity of B-cell activation on boosting with a recall antigen, and a parallelism between the appearance of activated B cells in the circulation and of IgG anti-TT synthesis by the subject as a whole.     

Differential synthesis of IgM and IgA anti-tetanus toxoid antibody in vitro following in vivo booster immunization of humans.

The in vitro syntheses of IgM and IgG anti-tetanus toxoid antibody by human peripheral blood leukocytes were compared prior to and at various intervals following in vivo booster immunization with soluble tetanus toxoid. Prior to booster immunization, the in vitro synthesis of IgG anti-tetanus toxoid antibody by combinations of B cells and irradiated T lymphocytes was negligible following pokeweed mitogen stimulation. Within 2 weeks after booster immunization, the quantity of IgG anti-tetanus toxoid antibody synthesized in vitro increased 5- to 20-fold. There was no comparable increase in total IgG synthesis. In contrast to the synthesis of IgG antibody, in vitro synthesis of IgM anti-tetanus toxoid antibody occurred prior to booster immunization and did not increase significantly following booster immunization. This dichotomy in anti-tetanus antibody production was further demonstrated in an individual with common variable hypogammaglobulinemia whose lymphocytes synthesized normal quantities of total IgG, IgM, and IgM anti-tetanus toxoid antibody in vitro, but failed to synthesize IgG anti-tetanus antibody following in vivo booster immunization.     

Sodium periodate-induced suppressor T cells of the human in vitro antibody response

Combinations of T and B lymphocytes from normal individuals booster immunized 14–30 days previously with a combination of diphtheria and tetanus toxoids, synthesized IgG antitetanus toxoid, and IgG antidiphtheria toxoid antibodies when stimulated by pokeweed mitogen in vitro. The addition of 5 μg of soluble tetanus toxoid to the cultures during the first 2 days incubation resulted in greater than 90% suppression of the subsequent production of IgG antitetanus toxoid antibodies. The synthesis of IgM antitetanus toxoid antibodies, total IgG, total IgM, and IgG antidiphtheria toxoid antibodies were unaffected. Similarly, the addition of 5 μg of soluble diphtheria toxoid suppressed the synthesis of IgG antidiphtheria toxoid antibodies with no effect on the synthesis of IgG antitetanus antibodies. Allogeneic combinations of B and T lymphocytes were capable of mediating the suppression, and irradiation of the T cells caused only a partial and variable reversal of the suppression. The antigen-induced specific suppression of antibody synthesis could not be demonstrated in cultures stimulated with soluble T-cell-derived helper factors.     

IgG subclasses of anti-tetanus toxoid antibodies in adult and newborn normal subjects and in patients with systemic lupus erythematosus, Sjogren's syndrome, and drug-induced autoimmunity

The IgG subclasses of anti-tetanus toxoid (anti-TT) antibodies were quantitated in normal sera and sera from patients with rheumatic disease. Detection relied on a set of four mouse monoclonal antibodies, each of which showed specificity for the respective isotype, independent of gamma-chain allotype or light chain class of the human antibody. Approximately 90% of the total anti-TT activity in normal adults and patients with Sjogren's syndrome was IgG1. In addition, IgG4 antibodies were detected in one-half the samples, but IgG2 and IgG3 antibodies were observed in only two out of 36 sera. However, antibodies elicited in children immunized with TT were exclusively IgG1 and IgG3, with IgG4 antibodies detectable only at birth (presumably due to transplacental passage of antibody) in three of 12 children. In contrast to normal adults, patients with systemic lupus erythematosus (SLE) and drug-induced autoimmunity (DIA) had a more promiscuous isotype profile. IgG2 and/or IgG3 anti-TT antibodies were detected in 13 of 22 SLE patients and IgG3 antibodies in six of 11 patients with DIA. IgG4 anti-TT antibodies were predominant in seven of these 33 patients. These findings suggest that IgG isotypes may depend on the frequency of the stimulus, but global alterations in immunologic status as reflected in systemic autoimmune disease may override the homeostatic mechanisms that control isotype restriction.     

Autoreactive B cells in normal humans. Autoantibody production upon lymphocyte stimulation with autoantigen-xenoantigen conjugates

Mononuclear cells (MNC) from the blood of healthy individuals cannot be stimulated in vitro with the soluble autoantigen thyroglobulin (Tg). However, when Tg or pepsin fragments of Tg were coupled with a carrier protein, tetanus toxoid (TT), MNC from four healthy TT vaccinated individuals responded to the carrier-autoantigen conjugates by generating anti-Tg antibody forming cells (AFC), as shown in a spot enzyme-linked immunosorbent assay. Generation of anti-TT and anti-Tg AFC after stimulation with the conjugates required the donors to be boostered with TT. The autoantibodies were exclusively of the IgM class, in contrast to the carrier-specific anti-TT antibodies, which were predominantly of the IgG isotype. Activation of normal B cells to anti-Tg production was dependent on the presence of T cells in the cultures and required physical linkage of carrier and autoantigen: no anti-Tg AFC could be detected when MNC were stimulated with uncoupled combinations of Tg and TT. The autoreactive and the carrier-reactive B cells exhibited almost identical conjugate dose-response profiles, which suggest that they responded in a similar way to regulatory signals. These findings indicate that normal blood B cells are competent to respond to the autoantigen Tg in conjunction with signals originating from xeno-antigen-stimulated T cells.     

Maternal antibodies against tetanus toxoid do not inhibit potency of antibody responses to autologous antigen in newborn rhesus monkeys

Background

Our previous study suggested newborns have competent immune systems with the potential to respond to foreign antigens and vaccines. In this study, we examined infant immune responses to tetanus toxoid (TT) vaccination in the presence of maternal antibody to TT.

Methods

We examined changes in plasma levels of tetanus toxoid‐specific IgG1 (anti‐TT IgG1) in a total of eight infant rhesus macaques from birth through 6 months of age using a commercial Monkey Anti‐TT IgG1 ELISA kit.

Results

A significant correlation between anti‐TT IgG1 levels in vaccinated dams and their paired newborn infants was detected in control (non‐vaccinated) infants as previously reported. Maternal anti‐TT IgG1 levels declined rapidly within 1 month of birth in non‐vaccinated infants (n=4). In four infants vaccinated with TT at birth, we found two had rapid and robust antibody responses to vaccination. Interestingly, the other two first showed declining TT antibody levels for 2 weeks followed by increasing levels without additional vaccine boosts, indicating all four had good antibody responses to primary TT vaccination at birth, despite the presence of high levels of maternal antibodies to TT in all four infants.

Conclusions

Our data indicate that newborn macaques have competent immune systems that are capable of generating their own primary antibody responses to vaccination, at least to tetanus antigens. Maternal antibodies thus do not significantly impair antibody response to the vaccination, even when received on the day of birth in infant rhesus macaques.     

IgA and IgA diphtheria antitoxin responses from human tonsil lymphocytes.

Human tonsil lymphocytes were stimulated with diphtheria toxoid and then cultured in a Marbrook culture system so that antibodies could be measured in the culture supernatant. Specific antibodies were measured with excess radiolabeled antigen and antisera specific for each immunoglobulin class. Good IgG and IgA diphtheria antitoxin responses have been obtained and responding culture supernatants were shown to neutralize toxin. The relationship between antitoxin response in vitro and immunization of donors with toxoid was investigated. It was found that at least two immunizations after the age of 6 months were necessary to prime the tonsils for an in vitro antibody response. The IgG and IgA in culture supernatants were demonstrated by immunodiffusion and were measured by radioimmunoassay. By sucrose density gradient ultracentrifugation, it was shown that 40% of the IgA produced in the cultures was greater than 7S. Evidence was obtained that neither the IgA nor the specific IgA antitoxin bears secretory piece. It appears that human lymphocytes from tonsils produce polymer IgA in vitro without secretory piece.     

The novel arthritis-drug substance MCS-18 attenuates the antibody production in vivo

Influence of the novel arthritis drug-substance MCS-18 on the antibody (Ab) production against tetanus toxoid (TT) and diphtheria toxoid (DT) antigens was tested in vivo. Possible involvement of MCS-18 in Toll-like receptor (TLR) signalling pathway was further considered. MATERIALS AND METHODS: Immunization of male CD1 mice was done with subcutaneous injection of TT emulsified in Freund's Complete (FCA) or Incomplete Adjuvant (FIA) and mixed diversly with MCS-18 and different test substances. To investigate the influence of TLR activation Pam3Cys and lipopolysaccharide (LPS) emulsified in FIA were tested in combinations with MCS-18. Antibody production was analysed in vivo by tetanus- or diphtheria-toxin neutralization test. RESULTS: Immunogenicity of TT was significantly enhanced if administered together with FCA or TLR agonists Pam3Cys or LPS emulsified in FIA. It was shown that MCS-18 attenuated strongly the production of anti-TT Ab if administered together with the Ab elicitor FCA or TLR agonists in various combinations. MCS-18 was also active via oral administration. DISCUSSION: These findings suggest that MCS-18 could be a potent, non-toxic antagonist or a down-regulator of TLR signalling pathway. Investigations on further models are needed to establish ifMCS-18 may influence particularly the production of RA-specific auto-antibodies, too.     

Antibody-mediated coengagement of FcγRIIb and B cell receptor complex suppresses humoral immunity in systemic lupus erythematosus

Engagement of the low-affinity Ab receptor FcγRIIb downregulates B cell activation, and its dysfunction is associated with autoimmunity in mice and humans. We engineered the Fc domain of an anti-human CD19 Ab to bind FcγRIIb with high affinity, promoting the coengagement of FcγRIIb with the BCR complex. This Ab (XmAb5871) stimulated phosphorylation of the ITIM of FcγRIIb and suppressed BCR-induced calcium mobilization, proliferation, and costimulatory molecule expression of human B cells from healthy volunteers and systemic lupus erythematosus (SLE) patients, as well as B cell proliferation induced by LPS, IL-4, or BAFF. XmAb5871 suppressed humoral immunity against tetanus toxoid and reduced serum IgM, IgG, and IgE levels in SCID mice engrafted with SLE or healthy human PBMC. XmAb5871 treatment also increased survival of mice engrafted with PBMC from a unique SLE patient. Unlike anti-CD20 Ab, coengagement of FcγRIIb and BCR complex did not promote B cell depletion in human PBMC cultures or in mice. Thus, amplification of the FcγRIIb inhibitory pathway in activated B cells may represent a novel B cell-targeted immunosuppressive therapeutic approach for SLE and other autoimmune diseases that should avoid the complications associated with B cell depletion.