Upregulated selenoprotein I during lipopolysaccharide-induced B cell activation promotes lipidomic changes and is required for effective differentiation into IgM-secreting plasma B cells.

The mechanisms driving metabolic reprogramming during B cell activation are unclear, particularly roles for enzymatic pathways involved in lipid remodeling. We found that murine B cell activation with lipopolysaccharide (LPS) led to a 1.6-fold increase in total lipids that included higher levels of phosphatidylethanolamine (PE) and plasmenyl PE. Selenoprotein I (SELENOI) is an ethanolamine phospholipid transferase involved in the synthesis of both PE and plasmenyl PE, and SELENOI expression was also upregulated during activation. Selenoi knockout (KO) B cells exhibited decreased levels of plasmenyl PE, which plays an important antioxidant role. Lipid peroxidation was measured and found to increase ∼2-fold in KO vs. wild-type (WT) B cells. Cell death was not impacted by KO in LPS-treated B cells and proliferation was only slightly reduced, but differentiation into CD138 + Blimp-1+ plasma B cells was decreased ∼2-fold. This led to examination of B cell receptors important for differentiation that recognize the ligand B cell activating factor, and levels of TACI (transmembrane activator, calcium-modulator, and cytophilin ligand interactor) (CD267) were significantly decreased on KO B cells compared with WT control cells. Vaccination with ovalbumin/adjuvant led to decreased ovalbumin-specific immunoglobulin M (IgM) levels in sera of KO mice compared with WT mice. Real-time polymerase chain reaction analyses revealed a decreased switch from surface to secreted IgM in spleens of KO mice induced by vaccination or LP-BM5 retrovirus infection. Overall, these findings detail the lipidomic response of B cells to LPS activation and reveal the importance of upregulated SELENOI for promoting differentiation into IgM-secreting plasma B cells.

Superoxide Dismutase Prevents SARS-CoV-2-Induced Plasma Cell Apoptosis and Stabilizes Specific Antibody Induction.

The infection of coronavirus disease (COVID-19) seriously threatens human life. It is urgent to generate effective and safe specific antibodies (Abs) against the pathogenic elements of COVID-19. Mice were immunized with SARS-CoV-2 spike protein antigens: S ectodomain-1 (CoV, in short) mixed in Alum adjuvant for 2 times and boosted with CoV weekly for 6 times. A portion of mice were treated with Maotai liquor (MTL, in short) or/and heat stress (HS) together with CoV boosting. We observed that the anti-CoV Ab was successfully induced in mice that received the CoV/Alum immunization for 2 times. However, upon boosting with CoV, the CoV Ab production diminished progressively; spleen CoV Ab-producing plasma cell counts reduced, in which substantial CoV-specific Ab-producing plasma cells (sPC) were apoptotic. Apparent oxidative stress signs were observed in sPCs; the results were reproduced by exposing sPCs to CoV in the culture. The presence of MTL or/and HS prevented the CoV-induced oxidative stress in sPCs and promoted and stabilized the CoV Ab production in mice in re-exposure to CoV. In summary, CoV/Alum immunization can successfully induce CoV Ab production in mice that declines upon reexposure to CoV. Concurrent administration of MTL/HS stabilizes and promotes the CoV Ab production in mice.

Colloidal Manganese Salt Improves the Efficacy of Rabies Vaccines in Mice, Cats, and Dogs.

Rabies, caused by rabies virus (RABV), remains a serious threat to public health in most countries worldwide. At present, the administration of rabies vaccines has been the most effective strategy to control rabies. Herein, we evaluate the effect of colloidal manganese salt (Mn jelly [MnJ]) as an adjuvant of rabies vaccine in mice, cats, and dogs. The results showed that MnJ promoted type I interferon (IFN-I) and cytokine production in vitro and the maturation of dendritic cells (DCs) in vitro and in vivo. Besides, MnJ serving as an adjuvant for rabies vaccines could significantly facilitate the generation of T follicular helper (Tfh) cells, germinal center (GC) B cells, plasma cells (PCs), and RABV-specific antibody-secreting cells (ASCs), consequently improve the immunogenicity of rabies vaccines, and provide better protection against virulent RABV challenge. Similarly, MnJ enhanced the humoral immune response in cats and dogs as well. Collectively, our results suggest that MnJ can facilitate the maturation of DCs during rabies vaccination, which can be a promising adjuvant candidate for rabies vaccines. IMPORTANCE Extending the humoral immune response by using adjuvants is an important strategy for vaccine development. In this study, a novel adjuvant, MnJ, supplemented in rabies vaccines was evaluated in mice, cats, and dogs. Our results in the mouse model revealed that MnJ increased the numbers of mature DCs, Tfh cells, GC B cells, PCs, and RABV-specific ASCs, resulting in enhanced immunogenicity and protection rate of rabies vaccines. We further found that MnJ had the same stimulative effect in cats and dogs. Our study provides the first evidence that MnJ serving as a novel adjuvant of rabies vaccines can boost the immune response in both a mouse and pet model.

Dietary Supplementation With Eicosapentaenoic Acid Inhibits Plasma Cell Differentiation and Attenuates Lupus Autoimmunity.

Accumulating evidence suggests that cholesterol accumulation in leukocytes is causally associated with the development of autoimmune diseases. However, the mechanism by which fatty acid composition influences autoimmune responses remains unclear. To determine whether the fatty acid composition of diet modulates leukocyte function and the development of systemic lupus erythematosus, we examined the effect of eicosapentaenoic acid (EPA) on the pathology of lupus in drug-induced and spontaneous mouse models. We found that dietary EPA supplementation ameliorated representative lupus manifestations, including autoantibody production and immunocomplex deposition in the kidneys. A combination of lipidomic and membrane dynamics analyses revealed that EPA remodels the lipid composition and fluidity of B cell membranes, thereby preventing B cell differentiation into autoantibody-producing plasma cells. These results highlight a previously unrecognized mechanism by which fatty acid composition affects B cell differentiation into autoantibody-producing plasma cells during autoimmunity, and imply that EPA supplementation may be beneficial for therapy of lupus.

Comparative Assessment of Leukocyte Infiltrate Composition in the Uterine and Vaginal Tissues in Rats with Experimental Endomyometritis Treated with Interferon-γ at Different Times of the Day.

The cell composition of leukocyte infiltrates in the endometrium, myometrium, and vaginal walls was studied in Wistar rats with modeled chronic endomyometritis after administration of IFNγ (0.1 µg/100 g body weight) in different daily regimens (10.00 or 20.00). Morning injections of this cytokine ameliorated inflammatory infiltration of the uterine wall and vagina, but increased the content of neutrophils in the endometrium. Evening cytokine injections reduced neutrophilic infiltration, enhanced mononuclear infiltration, and had no effect on plasmacytic infiltration of the uterine and vaginal walls. In the vaginal wall, both IFNγ administration schedules decreased neutrophil content. The data indicate the necessity to take into account the circadian rhythms in IFN therapy.

A Pauci-Immune Synovial Pathotype Predicts Inadequate Response to TNFα-Blockade in Rheumatoid Arthritis Patients.

Objectives: To assess whether the histopathological features of the synovium before starting treatment with the TNFi certolizumab-pegol could predict clinical outcome and examine the modulation of histopathology by treatment. Methods: Thirty-seven RA patients fulfilling UK NICE guidelines for biologic therapy were enrolled at Barts Health NHS trust and underwent synovial sampling of an actively inflamed joint using ultrasound-guided needle biopsy before commencing certolizumab-pegol and after 12-weeks. At 12-weeks, patients were categorized as responders if they had a DAS28 fall >1.2. A minimum of 6 samples was collected for histological analysis. Based on H&E and immunohistochemistry (IHC) staining for CD3 (T cells), CD20 (B cells), CD138 (plasma cells), and CD68 (macrophages) patients were categorized into three distinct synovial pathotypes (lympho-myeloid, diffuse-myeloid, and pauci-immune). Results: At baseline, as per inclusion criteria, DAS28 mean was 6.4 ± 0.9. 94.6% of the synovial tissue was retrieved from the wrist or a metacarpophalangeal joint. Histological pathotypes were distributed as follows: 58% lympho-myeloid, 19.4% diffuse-myeloid, and 22.6% pauci-immune. Patients with a pauci-immune pathotype had lower levels of CRP but higher VAS fatigue compared to lympho- and diffuse-myeloid. Based on DAS28 fall >1.2, 67.6% of patients were deemed as responders and 32.4% as non-responders. However, by categorizing patients according to the baseline synovial pathotype, we demonstrated that a significantly higher number of patients with a lympho-myeloid and diffuse-myeloid pathotype in comparison with pauci-immune pathotype [83.3% (15/18), 83.3 % (5/6) vs. 28.6% (2/7), p = 0.022) achieved clinical response to certolizumab-pegol. Furthermore, we observed a significantly higher level of post-treatment tender joint count and VAS scores for pain, fatigue and global health in pauci-immune in comparison with lympho- and diffuse-myeloid patients but no differences in the number of swollen joints, ESR and CRP. Finally, we confirmed a significant fall in the number of CD68+ sublining macrophages post-treatment in responders and a correlation between the reduction in the CD20+ B-cells score and the improvement in the DAS28 at 12-weeks. Conclusions: The analysis of the synovial histopathology may be a helpful tool to identify among clinically indistinguishable patients those with lower probability of response to TNFα-blockade.

The Yin and Yang of RNA surveillance in B lymphocytes and antibody-secreting plasma cells.

The random V(D)J recombination process ensures the diversity of the primary immunoglobulin (Ig) repertoire. In two thirds of cases, imprecise recombination between variable (V), diversity (D), and joining (J) segments induces a frameshift in the open reading frame that leads to the appearance of premature termination codons (PTCs). Thus, many B lineage cells harbour biallelic V(D)J-rearrangements of Ig heavy or light chain genes, with a productively-recombined allele encoding the functional Ig chain and a nonproductive allele potentially encoding truncated Ig polypeptides. Since the pattern of Ig gene expression is mostly biallelic, transcription initiated from nonproductive Ig alleles generates considerable amounts of primary transcripts with out-of-frame V(D)J junctions. How RNA surveillance pathways cooperate to control the noise from nonproductive Ig genes will be discussed in this review, focusing on the benefits of nonsense- mediated mRNA decay (NMD) activation during B-cell development and detrimental effects of nonsense-associated altered splicing (NAS) in terminally differentiated plasma cells. [BMB Reports 2019; 52(12): 671-678].

Pretransplant Desensitization with Costimulation Blockade and Proteasome Inhibitor Reduces DSA and Delays Antibody-Mediated Rejection in Highly Sensitized Nonhuman Primate Kidney Transplant Recipients.

BACKGROUND: Patients with broad HLA sensitization have poor access to donor organs, high mortality while waiting for kidney transplant, and inferior graft survival. Although desensitization strategies permit transplantation via lowering of donor-specific antibodies, the B cell-response axis from germinal center activation to plasma cell differentiation remains intact. METHODS: To investigate targeting the germinal center response and plasma cells as a desensitization strategy, we sensitized maximally MHC-mismatched rhesus pairs with two sequential skin transplants. We administered a proteasome inhibitor (carfilzomib) and costimulation blockade agent (belatacept) to six animals weekly for 1 month; four controls received no treatment. We analyzed blood, lymph node, bone marrow cells, and serum before desensitization, after desensitization, and after kidney transplantation. RESULTS: The group receiving carfilzomib and belatacept exhibited significantly reduced levels of donor-specific antibodies (P=0.05) and bone marrow plasma cells (P=0.02) compared with controls, with a trend toward reduced lymph node T follicular helper cells (P=0.06). Compared with controls, carfilzomib- and belatacept-treated animals had significantly prolonged graft survival (P=0.02), and renal biopsy at 1 month showed significantly reduced antibody-mediated rejection scores (P=0.02). However, four of five animals with long-term graft survival showed gradual rebound of donor-specific antibodies and antibody-mediated rejection. CONCLUSIONS: Desensitization using proteasome inhibition and costimulation blockade reduces bone marrow plasma cells, disorganizes germinal center responses, reduces donor-specific antibody levels, and prolongs allograft survival in highly sensitized nonhuman primates. Most animals experienced antibody-mediated rejection with humoral-response rebound, suggesting desensitization must be maintained after transplantation using ongoing suppression of the B cell response.

A Recombinant Rabies Virus Expressing Fms-like Tyrosine Kinase 3 Ligand (Flt3L) Induces Enhanced Immunogenicity in Mice.

Rabies is a zoonotic disease that still causes 59,000 human deaths each year, and rabies vaccine is the most effective way to control the disease. Our previous studies suggested that the maturation of DC plays an important role in enhancing the immunogenicity of rabies vaccine. Flt3L has been reported to own the ability to accelerate the DC maturation, therefore, in this study, a recombinant rabies virus expressing mouse Flt3L, designated as LBNSE-Flt3L, was constructed, and its immunogenicity was characterized. It was found that LBNSE-Flt3L could enhance the maturation of DC both in vitro and in vivo, and significantly more TFH cells and Germinal Center B (GC B) cells were generated in mice immunized with LBNSE-Flt3L than those immunized with the parent virus LBNSE. Consequently, expressing of Flt3L could elevate the level of virus-neutralizing antibodies (VNA) in immunized mice which provides a better protection from a lethal rabies virus challenge. Taken together, our study extends the potential of Flt3L as a good adjuvant to develop novel rabies vaccine by enhancing the VNA production through activating the DC-TFH-GC B axis in immunized mice.

The origin of prostate gland-secreted IgA and IgG.

The prostate secretes immunoglobulin (Ig) A (IgA) and IgG; however, how immunoglobulins reach the secretion, where the plasma cells are located, whether immunoglobulins are antigen-specific and where activation of the adaptive response occurs are still unknown. Immune cells, including CD45RA+ cells, were scattered in the stroma and not organized mucosae-associated lymphoid-tissue. IgA (but not IgG) immunostaining identified stromal plasma cells and epithelial cells in non-immunized rats. Injected tetramethylrhodamine-IgA transcytosed the epithelium along with polymeric immunoglobulin receptor. Oral immunization with ovalbumin/mesopourous SBA-15 silica adjuvant resulted in more stromal CD45RA+/IgA+ cells, increased content of ovalbumin-specific IgA and IgG, and the appearance of intraepithelial CD45RA+/IgG+ cells. An increased number of dendritic cells that cooperate in other sites with transient immunocompetent lymphocytes, and the higher levels of interleukin-1ß, interferon-γ and transforming growth factor-ß, explain the levels of specific antibodies. Nasal immunization produced similar results except for the increase in dendritic cells. This immunomodulatory strategy seems useful to boost immunity against genitourinary infections and, perhaps, cancer.

The specialized proresolving mediator 17-HDHA enhances the antibody-mediated immune response against influenza virus: a new class of adjuvant?

Influenza viruses remain a critical global health concern. More efficacious vaccines are needed to protect against influenza virus, yet few adjuvants are approved for routine use. Specialized proresolving mediators (SPMs) are powerful endogenous bioactive regulators of inflammation, with great clinical translational properties. In this study, we investigated the ability of the SPM 17-HDHA to enhance the adaptive immune response using an OVA immunization model and a preclinical influenza vaccination mouse model. Our findings revealed that mice immunized with OVA plus 17-HDHA or with H1N1-derived HA protein plus 17-HDHA increased Ag-specific Ab titers. 17-HDHA increased the number of Ab-secreting cells in vitro and the number of HA-specific Ab-secreting cells present in the bone marrow. Importantly, the 17-HDHA-mediated increased Ab production was more protective against live pH1N1 influenza infection in mice. To our knowledge, this is the first report on the biological effects of ω-3-derived SPMs on the humoral immune response. These findings illustrate a previously unknown biological link between proresolution signals and the adaptive immune system. Furthermore, this work has important implications for the understanding of B cell biology, as well as the development of new potential vaccine adjuvants.

Regulation of intestinal IgA responses by dietary palmitic acid and its metabolism.

Enhancement of intestinal IgA responses is a primary strategy in the development of oral vaccine. Dietary fatty acids are known to regulate host immune responses. In this study, we show that dietary palmitic acid (PA) and its metabolites enhance intestinal IgA responses. Intestinal IgA production was increased in mice maintained on a PA-enriched diet. These mice also showed increased intestinal IgA responses against orally immunized Ag, without any effect on serum Ab responses. We found that PA directly stimulates plasma cells to produce Ab. In addition, mice receiving a PA-enriched diet had increased numbers of IgA-producing plasma cells in the large intestine; this effect was abolished when serine palmitoyltransferase was inhibited. These findings suggest that dietary PA regulates intestinal IgA responses and has the potential to be a diet-derived mucosal adjuvant.

B7-H1 expression on non-B and non-T cells promotes distinct effects on T- and B-cell responses in autoimmune arthritis.

The immune system has developed several regulatory mechanisms to maintain homeostasis of adaptive immune responses. T-cell programmed death (PD)-1 recognition of B7-H1 (PD-L1) expressed on APC and non-lymphoid tissue regulates T-cell activation. We show that B7-H1(-/-) mice exhibit exacerbated proteoglycan (PG)-induced arthritis and increased Th-1 CD4(+) T-cell responses. Unexpectedly, the PG-specific antibody response in B7-H1(-/-) mice was diminished. A reduction in the number of peanut agglutinin(+) GC coincided with a decrease in CD19(+) GL-7(+) CD95(+) GC B cells that was a result of increased caspase-induced apoptosis. The percent of CD38(+) CD138(+) emerging plasma cells was decreased. B7-H1(-/-) mice exhibited an increased frequency of CD4(+) PD-1(hi) CXCR5(hi) ICOS(hi) CD62L(lo) T follicular helper cells that displayed a hyperactive phenotype with increased expression of mRNA transcripts for Bcl6, IL-21, and the apoptosis-inducer molecule FasL. In cell transfer of B7-H1(-/-) cells into SCID mice, non-B and non-T cells were sufficient to normalize the antibody response, T-cell hyperactivity, and the development of PG-induced arthritis. These findings indicate that B7-H1 on non-B and non-T cells signals through PD-1 on T effector cells to prevent excessive activation and reduce autoimmune arthritis. Furthermore, these findings demonstrate a novel role for B7-H1 expression in promoting B-cell survival by regulating the activation of T follicular helper cell.

E2A-positive gastric MALT lymphoma has weaker plasmacytoid infiltrates and stronger expression of the memory B-cell-associated miR-223: possible correlation with stage and treatment response.

Extranodal marginal-zone lymphoma of mucosa-associated lymphoid tissue of the stomach (gastric MALT lymphoma) is derived from memory B cells of the marginal zone. Normal memory B cells do not express markers of germinal-center B cells, such as E2A (immunoglobulin enhancer-binding factor E12/E47), B-cell chronic lymphocytic leukemia/lymphoma 6 (BCL6), or activation-induced cytidine deaminase (AID). E2A is a transcription factor that induces somatic hypermutations and blocks plasma cell differentiation. In 50 stage-I(E)/II(E1) gastric MALT lymphomas, we confirmed that all cases were BCL6(-)/AID(-), but a subset (50%, 25/50) was E2A(+). As E2A(-) and E2A(+) gastric MALT lymphomas had similar numbers of somatic hypermutations without intraclonal variations, which implied an origin from memory B cells, the expression of E2A was best regarded as a marker of aberrant follicular differentiation. Although the status of somatic hypermutation was not affected by E2A, E2A(+) gastric MALT lymphoma showed less plasmacytoid infiltrates and higher expressions of miRNA-223, a microRNA associated with memory B cells. Clinically, E2A(+) gastric MALT lymphomas were more likely to spread to perigastric lymph nodes and were less responsive to Helicobacter eradication therapy than were E2A(-) gastric MALT lymphomas. Taken together, aberrant E2A expression is a diagnostic feature of a subtype of gastric MALT lymphoma with weaker plasmacytoid infiltrates and stronger miR-223 expression. A prospective study would be necessary to verify the association between E2A expression and a poor response to Helicobacter eradication therapy.

Dietary glutamine and oral antibiotics each improve indexes of gut barrier function in rat short bowel syndrome.

Short bowel syndrome (SBS) is associated with gut barrier dysfunction. We examined effects of dietary glutamine (GLN) or oral antibiotics (ABX) on indexes of gut barrier function in a rat model of SBS. Adult rats underwent a 60% distal small bowel + proximal colonic resection (RX) or bowel transection (TX; control). Rats were pair fed diets with or without l-GLN for 20 days after operation. Oral ABX (neomycin, metronidazole, and polymyxin B) were given in some RX rats fed control diet. Stool secretory immunoglobulin A (sIgA) was measured serially. On day 21, mesenteric lymph nodes (MLN) were cultured for gram-negative bacteria. IgA-positive plasma cells in jejunum, stool levels of flagellin- and lipopolysaccharide (LPS)-specific sIgA, and serum total, anti-flagellin- and anti-LPS IgG levels were determined. RX caused gram-negative bacterial translocation to MLN, increased serum total and anti-LPS IgG and increased stool total sIgA. After RX, dietary GLN tended to blunt bacterial translocation to MLN (-29%, P = NS) and significantly decreased anti-LPS IgG levels in serum, increased both stool and jejunal mucosal sIgA and increased stool anti-LPS-specific IgA. Oral ABX eliminated RX-induced bacterial translocation, significantly decreased total and anti-LPS IgG levels in serum, significantly decreased stool total IgA and increased stool LPS-specific IgA. Partial small bowel-colonic resection in rats is associated with gram-negative bacterial translocation from the gut and a concomitant adaptive immune response to LPS. These indexes of gut barrier dysfunction are ameliorated or blunted by administration of dietary GLN or oral ABX, respectively. Dietary GLN upregulates small bowel sIgA in this model.

Deficient TACI expression on B lymphocytes of newborn mice leads to defective Ig secretion in response to BAFF or APRIL.

Capsular polysaccharides of encapsulated bacteria do not induce immune response in newborns and the mechanism for this unresponsiveness is not clear. In adults, transmembrane activator and calcium-modulator and cyclophilin [corrected] ligand interactor (TACI) is a TNFR family member molecule with a pivotal role in Ab responses against polysaccharide vaccines. We investigated the expression and the functions of the TNF family cytokines, B cell-activating factor of the TNF family (BAFF) and a proliferation-inducing ligand (APRIL), and their receptors in newborn mice and found that TACI expression on B lymphocytes was dramatically reduced (p < 0.0001) in newborns as compared with adults. More importantly, TACI ligands BAFF or APRIL were unable to induce IgA/IgG/IgM secretion from newborn B lymphocytes. Additionally, TACI expression seems to be important in plasma cell development. Indeed, in contrast to adults, stimulation of newborn B lymphocytes with BAFF or APRIL did not result in up-regulation of CD138 expression. In vitro or in vivo exposure of newborn B lymphocytes to oligodeoxynucleotides (CpG ODN) led to up-regulation of TACI expression on newly formed, follicular, and marginal zone as well as B1 B lymphocyte populations, and rendered them responsive to BAFF- or APRIL-mediated CD138 expression and IgA/IgG secretion. Finally, immunization of newborn BALB/c mice but not TACI knockout mice with CpG ODN containing (4-hydroxy-3-nitrophenyl)acetyl-Ficoll led to development of IgG Abs against (4-hydroxy-3-nitrophenyl)acetyl. These findings demonstrate that low TACI expression may be a critical factor that determines the susceptibility of newborns to infections with encapsulated bacteria and the impaired immunogenicity of polysaccharide vaccines. Finally, CpG ODNs may correct deficient newborn response to polysaccharide vaccines by up-regulating TACI.

A high-affinity monoclonal anti-IgE antibody for depletion of IgE and IgE-bearing cells.

BACKGROUND: We have identified a monoclonal anti-human immunoglobulin E (IgE) antibody, which recognizes FcepsilonRI-bound IgE and prevents binding of IgE to FcepsilonRI. In this study, we assessed the binding kinetics and affinity of monoclonal antibody 12 (mAb12) for IgE and investigated whether mAb12 can be used for depletion of IgE and isolation of IgE-bearing cells from peripheral blood. METHODS: Binding kinetics and affinity for IgE were studied using Biacore surface plasmon resonance technique experiments. IgE antibodies were depleted from serum using sepharose-coupled mAb12 and IgE-bearing cells were enriched from heparinized blood samples with mAb12. The extent and biological relevance of IgE depletion were studied by quantitative IgE measurements and basophil histamine release experiments. Specific binding of mAb12 to IgE-bearing cells (basophils, mast cells, IgE-secreting plasma cells) was demonstrated by FACS. RESULTS: Monoclonal antibody 12 shows rapid association (k(a) = 5.46e5/Ms) with IgE, almost no dissociation (k(d) = 8.8e-5/s) and an affinity for IgE (K(D) = 1.61e-10 M), which is as high as that of FcepsilonRI. Immobilized mAb12 could be used to deplete IgE antibodies and isolate IgE-bearing cells from peripheral blood in a single-step procedure. CONCLUSIONS: Monoclonal antibody 12 is a high affinity anti-human IgE antibody, which efficiently removes IgE and IgE-bearing cells from peripheral blood and may thus be used for extracorporeal depletion of IgE and IgE-bearing cells.

The effect of selenium and vitamin E on the lymphocytes and immunoglobulin-containing plasma cells in the lymphoid organ and mucosa-associated lymphatic tissues of broiler chickens.

The present research has been designed to understand the effect of selenium and vitamin E on the lymphocyte and changes in the frequency of Ig-containing plasma cells in the lymphatic organ and ileum (representative organ for mucosa-associated lymphatic tissues) of different postnatal stages of Kasilla broiler chickens. A routine haematoxylin and eosin (H and E) stain were used to study the histology of the lymphocytic changes, and indirect immunoperoxidase staining method was performed for the study of the distributional and dynamical changes of the Ig-containing plasma cells within the lymphatic tissues and in the ileum of control broilers and in the broilers supplemented with different concentration of selenium and vitamin E in the diet. Histologically, the population of lymphocytes decreased in the lobules of the thymus, medulla of bursal follicles, splenic masses, lymphatic nodules of the cecal tonsil, and villi of the ilium in 0.1 mg and 0.5 mg selenium supplemented broilers in comparison with the control. The population of these cells was found to increase in 150 mg and 300 mg vitamin E supplemented chickens in the present study. In the spleen IgG- and the IgM-containing plasma cells were more than IgA-containing plasma cells. In contrast, in the cecal tonsil and ileum IgA-containing plasma cells were more than IgG- and IgM-containing plasma cells. The frequency of these immunopositive cells were decreased in 0.1 mg and 0.5 mg selenium supplementated chickens, and increased their frequency in the chickens supplemented with 150 mg and 300 mg vitamin E. In the spleen the frequency of IgM-containing plasma cells and both in the cecal tonsil and ileum, the IgG-containing plasma cells were more decreased by selenium supplementation which restored in their population by vitamin E supplementation.