Fc Receptor Gene Research Articles

Impact of Fc receptors and host characteristics on myeloid phagocytic response to rituximab-treated 3D-cultured B-cell lymphoma.

Antibody-based immunotherapy is successful in treating cancer, but its effectiveness varies among patients. Therefore, understanding myeloid phagocytic responses to therapeutic antibodies is critical. Immunoglobulin Fc receptors and host characteristics were evaluated in phagocytosis of 3D-cultured CD20+ B-cell lymphoma (spheroids) treated with different anti-CD20 rituximab (RTX) monoclonal antibody isotypes. Monocytes from healthy donors of different ages and sexes were isolated, and their Fc receptors for IgG (FcγRI, FcγRIIa, FcγRIIIa) and IgA (FcαRI) were determined, as well as Fc receptor gene polymorphisms. Antibody-dependent phagocytosis was assessed using flow cytometry, confocal imaging, and Fc receptor blocking. RTX isotypes showed varying efficacy in stimulating the phagocytosis of spheroids. RTX-IgG3 proved to be the most efficient, followed by RTX-IgG1. Monocytes infiltrated RTX-treated spheroids at the periphery but migrated also into the core when stimulated with RTX-IgG3. Blocking FcγRI or FcγRIIa, but not FcγRIIIa, with antibodies inhibited RTX-IgG1 and RTX-IgG3-mediated phagocytosis. Monocytes from younger women demonstrated higher FcγRI and FcγRIIa levels compared to older women, while older men displayed increasing FcγRI and FcγRIIIa levels compared to younger men. Monocytes from younger women displayed greater phagocytic activity compared to older women, while older men had better IgG-mediated phagocytosis than younger men. Single Fc receptor levels, or FcγRIIa and FcγRIIIa genetic variants, had a low correlation with phagocytic intensity, likely as a result of multiple engagements of Fcreceptors for IgG-mediated phagocytosis. In conclusion, antibody isotype, Fc receptors, age, and sex influence tumor phagocytosis. This study exposes the relationship between host traits and the efficacy of therapeutic antibodies, providing insights into cancer immunotherapy treatment.

Somatic Mutations Associated with IgVH4-34 FR1 Region Unmutated QW and Avy Motifs in DLBCL Patients

There is increasing evidence for antigen-driven B-cell receptor (BCR) signalling in diffuse large B-cell lymphoma (DLBCL) and other lymphoid malignancies. This includes antigens from infections e.g.Helicobacter pyloriand Hepatitis C virus, but it is theorised that self-antigens may play a major role in some cases of lymphoid malignancy. IgVH4-34 demonstrates intrinsic autoreactivity to self-antigens on red cells, which appears to be largely mediated by two motifs within the first framework region (FR1); Q6W7 and A24V25Y26. These motifs work together to for a hydrophobic patch which determines red cell antigen binding and are frequently mutated away from self-reactivity in normal B cells. IgVH4-34 has been reported to be over-represented in DLBCL compared with expression in normal B cells. We therefore sought to identify IgVH4-34 DLBCL cases from a local cohort and to screen them for Q6W7 and A24V25Y26 motifs expecting them to be less frequently mutated in DLBCL compared with normal B cells.We also aimed to screen V4-34 cases for associated somatic mutations in other genes using high-throughput sequencing. DLBCL patient samples were obtained via the Haematology Research Tissue Bank (HRTB) in Canberra, Australia, and the Victoria Cancer BioBank. Forty-eight Formalin-Fixed, Paraffin-Embedded (FFPE) samples and 26 fresh frozen samples were screened. All samples were collected at the time of diagnosis. Patients were treated with standard chemoimmunotherapy approaches. IgVH 4-34 gene sequences were determined using an IgVH4 family-specific leader primer in combination with a JH consensus reverse primer. The IgVH region was then sequenced using Sanger sequencing. Sequences were analyzed using the IgBLAST database (National Centre for Biotechnology Information). DNA extracted from FFPE samples generally proved to have low concentration and fragmented DNA. Only 1 IgVH4-34 sequence was obtained from FFPE tissue. Five samples sequenced from fresh tissue were identified as using IgVH4-34. Using Hans criteria, it was possible to classify 3 of the 6 cases as germinal center (GC) and 1 as non-GC origin. Using fresh samples, we estimated the frequency of IgVH4-34 cases at 23%. Within FR1, Q6W7 was unmutated in all 6 samples. One sample had mutations in the A24V25Y26 motif resulting in a change to A24V25F26. The other 5 samples (83.3%) had unmutated AVY motifs. We extracted genomic DNA from and performed next generation sequencing on the 5 samples with unmutated Q6W7 and A24V25Y26 motifs using a customized capture library (SureSelectXT Target Enrichment System, Aqilent Technologies) covering genes involved in lymphomagenesis. The purified libraries were sequenced on the Illumina NextSeq500 platform at AGRF (Australian Genome Research Facility, Australia). Several genes (FCGR3A,NOTCH2andNOTCH2NLR) had mutations in all 5 samples.FCGR3Ais an IgG Fc receptor gene, and mutations inFCGR3Ahave previously been linked to systemic lupus erythematosus (SLE).NOTCH2pathway genes are frequently mutated in DLBCL.CREBBPwas mutated in four of the five samples. Mutations inCREBBPhave previously been linked with DLBCL development and regulation of immune responses. We identified high rates of IgVH4-34 (23%) in our cohort of fresh samples as previously reported. Further, we noted preservation of the Q6W7 and A24V25Y26 motifs in IgVH4-34-expressing DLBCL. This over-representation of unmutated FR1 motifs suggests that the ability to recognise self-antigens likely provides important ongoing BCR signalling that promotes survival in DLBCL. This study also highlights the difficulties in conducting DNA-based research on FFPE clinical samples which have not been collected for research purposes and the importance of tissue banking fresh samples. Studies are currently being conducted into the efficacy of BCR pathway inhibitors e.g. ibrutinib in the treatment of DLBCL and testing for unmutated IgVH4-34 FR1 motifs may present a method to predict patients who are more likely to respond. Mutations in genes such as FCGR3A,NOTCH2andCREBBPmay work in conjunction with the preserved QW and AVY motifs to promote lymphomagenesis in IgVH4-34-expressing B cells and may present targets for future research into treatment therapies. Figure Disclosures Talaulikar: Roche:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Janssen:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Amgen:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Takeda:Research Funding.

The Invertebrate Antibody

Introduction Many researchers don’t believe in our works: they speak we are wrong when we evoke the Invertebrate Antibody...BUT: Discussion We have discovered, in the past, the sea star lymphocytes ( B and T sea star lymphocytes : cf Fig 1,2) : these cells of 4-5µ in diameter are smaller than Vertebrate lymphocytes And ...We discovered recently the IPA (Invertebrate Primitive Antibody) with the sea star IGKAPPA gene with IG sites (Meta Gene 2013). Therefore genomic data assert the evidence of primitive antibody in Echinodermata. Furthermore, we find MHC genes class I and class II in 2019 and Fab gene, Fc receptor gene in these Invertebrates

Morphology, Immunology of Antedon Bifida (Echinodermata)

Antedon bifida, belongs to the class of Crinoïds. It’s an ancestral ECHINODERMATA. The body is a concave disc surrounded by ten pinnately divided arms, giving it a fem-like appearance. It possesses an axial organ similar to the sea star one : a primitive immune organ. We discover in it : 1) An IGKAPPA Gene recalling the IPA (Invertebrate Primitive Antibody) 3) A Fc receptor gene witch matches with human Fc gene 4) At Last MHC genes.

INFLUENCE OF EXPRESSION OF THE NEONATAL FC-RECEPTOR (FCRN) ON THE SENSITIVITY OF THE CELLS TO NON-PATHOGENIC HUMAN ENTEROVIRUSES

In this work, the influence of the expression levels of the neonatal Fc receptor (FcRn) on the sensitivity of the human transformed and tumor cells to 15 non-pathogenic strains of human enteroviruses was shown. The Complete inactivation of the neonatal fc receptor gene FCGRT in cells led to loss of the sensitivity to Echoviruses 1, 6, 7, 11, 12, 25, 30, enterovirus 75.

HLA Class I-sensitized Renal Transplant Patients Have Antibody Binding to SLA Class I Epitopes.

Highly sensitized patients are difficult to match with suitable renal allograft donors and may benefit from xenotransplant trials. We evaluate antibody binding from sensitized patients to pig cells and engineered single allele cells to identify anti-human leukocyte antigen (HLA) antibody cross-species reactivity with swine leukocyte antigen (SLA). These novel testing strategies assess HLA/SLA epitopes and antibody-binding patterns and introduce genetic engineering of SLA epitopes. Sensitized patient sera were grouped by calculated panel reactive antibody and luminex single antigen reactivity profile and were tested with cloned GGTA1/CMAH/B4GalNT2 glycan knockout porcine cells. Pig reactivity was assessed by direct flow cytometric crossmatch and studied following elution from pig cells. To study the antigenicity of individual class I HLA and SLA alleles in cells, irrelevant sera binding to lymphoblastoid cells were minimized by CRISPR/Cas9 elimination of endogenous class I and class II HLA, B-cell receptor, and Fc receptor genes. Native HLA, SLA, and mutants of these proteins after mutating 144K to Q were assessed for antibody binding. Those with predominately anti-HLA-B&C antibodies, including Bw6 and Bw4 sensitization, frequently have low pig reactivity. Conversely, antibodies eluted from porcine cells are more commonly anti-HLA-A. Single HLA/SLA expressing engineered cells shows variable antigenicity and mutation of 144K to Q reduces antibody binding for some sensitized patients. Anti-HLA antibodies cross-react with SLA class I in predictable patterns, which can be identified with histocompatibility strategies, and SLA class I is a possible target of genetic engineering.

Effect of Fc Receptor Genetic Diversity on HIV-1 Disease Pathogenesis

Fc receptor (FcR) genes collectively have copy number and allelic polymorphisms that have been implicated in multiple inflammatory and autoimmune diseases. This variation might also be involved in etiology of infectious diseases. The protective role of Fc-mediated antibody-function in HIV-1 immunity has led to the investigation of specific polymorphisms in FcR genes on acquisition, disease progression, and vaccine efficacy in natural history cohorts. The purpose of this review is not only to explore these known HIV-1 host genetic associations, but also to re-evaluate them in the context of genome-wide data. In the current era of effective anti-retroviral therapy, the potential impact of such variation on post-treatment cohorts cannot go unheeded and is discussed here in the light of current findings. Specific polymorphisms associating with HIV-1 pathogenesis have previously been genotyped by assays that captured only the single-nucleotide polymorphism (SNP) of interest without relative information of neighboring variants. With recent technological advances, variation within these genes can now be characterized using next-generation sequencing, allowing precise annotation of the whole chromosomal region. We herein also discuss updates in the annotation of common FcR variants that have been previously associated with HIV-1 pathogenesis.

The Sea Star Igkappa Gene and The Ophuirid Igkappa Gene Vaccinations to HRP (Horse-radish Peroxydase)

The main point of the sea star immunology, of the ophuirid immunology remain the discovery of the INVERTEBRATE PRIMITIVE ANTIBODY (IPA), the IGKAPPA GENES, with Ig sites which imply the COMPLEMENT SYSTEM, to be initiated: 9 component genes from C1 to C9 have been updated these last years, in sea star genome, in ophuirid one. These primitive antibodies were obtained after immunizations to the enzyme HRP (Horse-radish peroxydase). It is the first time we observe vaccinations in invertebrates. We have discovered, for the first time also, in these same Invertebrate a FC receptor gene, a Fab gene which corroborate the presence of IPA. The transcriptomes are given. It is the first time, we can speak of Adaptative Immunity, in Echinoderms, in Invertebrates Since many years, even since a century long, the notion of Antibody was out of the speech of immunologists. To speak of that made you as an outlaw. It is time to look with genomic studies which confirm which assert now evidence that 3 classes of Echinoderms out of 5 possess an Igkappa gene, a FC receptor gene. I recall these classent: the Asterids with Asterias rubens, the Ophuirids with Ophiocomina nigra and the Crinoïds.

Evidence of immune genes in the crinoïd: Antedon bifida evidence of A.bifida Igkappa gene and a FC receptor one

Immuno-genomics studies realized in Echinodermata (Invertebrates) were surprising. 3 classes out of 5 Echinodermata presented an IGKappa gene and a Fc receptor gene. It was, first demonstrated, in Asterids and Ophuirids. It was, secondly clearly shown, in the ancestral Crinoid: Antedon bifida

Association of CD1 and FcγR gene polymorphisms with Guillain-Barré syndrome susceptibility: a meta-analysis.

CD1 and immunoglobulin G Fc receptor (FcγR) genes have been proposed to be involved in the pathogenesis of Guillain-Barré syndrome (GBS). However, results of different studies are conflicting. This meta-analysis aimed to systematically examine the association between CD1 and FcγR gene polymorphisms and GBS. A comprehensive literature search through PubMed, EmBase, ScienceDirect, and Cochrane Library was performed to identify all eligible studies. The strength of association was assessed by pooled odds ratios (ORs) and corresponding 95% confidence intervals (95% CI) in allelic, dominant, recessive, homozygous and heterozygous genetic models. Four case-control studies about polymorphisms of exon 2 in CD1A and CD1E genes and GBS risk and five studies (six cohorts) about FcγR gene polymorphisms and GBS risk were included in this meta-analysis. The association between exon 2 of CD1E gene polymorphism and GBS was marginally significant in Caucasians in allelic model (OR = 1.193, 95% CI = 1.001-1.423, P = 0.049). FcγRIIA gene polymorphism was significantly associated with GBS risk in Caucasians under allelic model (OR = 1.553, 95% CI = 1.018-2.368, P = 0.041) and dominant model (OR = 1.320, 95% CI = 1.027-1.697, P = 0.030). However, no significant association was found between polymorphisms in exon 2 of CD1A, FcγRIIIA and FcγRIIIB genes and GBS susceptibility. This meta-analysis suggested that FcγRIIA gene polymorphism may contribute to GBS risk in Caucasians and revealed a certain trend toward significance in the association of exon 2 of CD1E gene with GBS in Caucasians. Further studies with larger sample size are required to validate these results.

P4218Polymorphisms in Fc receptor genes are related to antibody-mediated rejection after heart transplantation

P4218Polymorphisms in Fc receptor genes are related to antibody-mediated rejection after heart transplantation

Dimerumic Acid and Deferricoprogen Activate Ak Mouse Strain Thymoma/Heme Oxygenase-1 Pathways and Prevent Apoptotic Cell Death in 6-Hydroxydopamine-Induced SH-SY5Y Cells.

Parkinson's disease (PD) is a neurodegenerative disorder, which can be modeled using the neurotoxin 6-hydroxydopamine (6-OHDA) to generate oxidative stress. Here, we studied the effects of the antioxidants deferricoprogen (DFC) and dimerumic acid (DMA), produced by rice fermented with Monascus purpureus NTU 568, on 6-OHDA-induced apoptosis in SH-SY5Y cells and their potential protective mechanisms. DMA and DFC inhibited 6-OHDA-induced apoptosis and cellular reactive oxygen species (ROS) in SH-SY5Y human neuroblastoma cells. Molecular analysis demonstrated associated upregulation of the Ak mouse strain thymoma (Akt), heme oxygenase-1 (HO-1), and signal-regulated kinase (ERK) pathways along with inhibited phosphorylation of c-Jun N-terminal kinase (JNK) and p38 pathways and altered homodimeric glycoprotein, N-methyl-d-aspartate (NMDA) receptor, and immunoglobulin Fc receptor gene expression. These results suggested that the neuroprotection elicited by DMA and DFC against 6-OHDA-induced neurotoxicity was associated with the Akt, MAPK, and HO-1 pathways via regulating the gene expression of NMDA receptor, homodimeric glycoprotein, and immunoglobulin Fc receptor.

Correction: Analysis of Response Elements Involved in the Regulation of the Human Neonatal Fc Receptor Gene (FCGRT).

Correction: Analysis of Response Elements Involved in the Regulation of the Human Neonatal Fc Receptor Gene (FCGRT).

Analysis of Response Elements Involved in the Regulation of the Human Neonatal Fc Receptor Gene (FCGRT)

Human epithelial, endothelial and PMA-differentiated THP-1 cell lines were used as model systems to study the transcriptional regulation of the human FCGRT gene encoding the alpha chain of hFcRn. The data obtained from site-directed mutagenesis in transient transfection experiments indicate that the Sp1 sites at positions -641, -635, and -313, CF1/YY1 elements at positions -586 and -357, and the AP-1 motif at -276 within the-660/-233 fragment of the human FCGRT promoter (hFCGRT) participate in the regulation of human FCGRT in all selected cell lines. However, their individual contribution to promoter activity is not equivalent. The Sp1 binding site at -313 and the AP-1 site at -276 are critical for the activity of the hFCGRT promoter in epithelial and endothelial cells. Moreover, the CF1/YY1 site at -586 in differentiated THP-1 cells, plays an essential role in the transcriptional activity of the promoter. In addition, the C/EBPbeta binding site at -497 of the hFCGRT promoter in epithelial and endothelial cells, and the C/EBPbeta motif located at -497 and -233 within the hFCGRT promoter in differentiated THP-1 cells may function as positive regulatory sequences in response to LPS or PMA stimulation. EMSA and supershift analyses showed that the functionally identified binding motifs in the hFCGRT promoter were able to specifically interact with their corresponding (Sp1, Sp2, Sp3, c-Fos, c-Jun, YY1, and C/EBPbeta or C/EBPdelta) transcription factors (TFs), suggesting their possible involvement in the regulation of the human FCGRT gene expression.

Identifying optimal biomarker combinations for treatment selection via a robust kernel method.

Treatment-selection markers predict an individual's response to different therapies, thus allowing for the selection of a therapy with the best predicted outcome. A good marker-based treatment-selection rule can significantly impact public health through the reduction of the disease burden in a cost-effective manner. Our goal in this article is to use data from randomized trials to identify optimal linear and nonlinear biomarker combinations for treatment selection that minimize the total burden to the population caused by either the targeted disease or its treatment. We frame this objective into a general problem of minimizing a weighted sum of 0-1 loss and propose a novel penalized minimization method that is based on the difference of convex functions algorithm (DCA). The corresponding estimator of marker combinations has a kernel property that allows flexible modeling of linear and nonlinear marker combinations. We compare the proposed methods with existing methods for optimizing treatment regimens such as the logistic regression model and the weighted support vector machine. Performances of different weight functions are also investigated. The application of the proposed method is illustrated using a real example from an HIV vaccine trial: we search for a combination of Fc receptor genes for recommending vaccination in preventing HIV infection.

AB0113 Association between functional fc receptor-like 3 (fcrl3) -169 c/t polymorphism and susceptibility to seropositive rheumatoid arthritis: a meta-analysis

BackgroundThe Fc receptor-like 3 gene (FCRL3) is located on chromosome 1q21, a region implicated in susceptibility to several autoimmune diseases by whole-genome linkage studies. The FCRL3 protein is an orphan...

FCGR2B and FCRLB Gene Polymorphisms Associated with IgA Nephropathy

BackgroundIgA nephropathy (IgAN) is a complex syndrome characterized by deposition of IgA and IgA containing immune complexes (ICs) composed of IgG and complement C3 proteins in the mesangial area of glomeruli. The low-affinity receptors for the Fc region of IgG (FcγRs) are involved in autoantibody/immune complex-induced organ injury as well as ICs clearance. The aim of the study was to associate multiple polymorphisms within FCGR gene locus with IgAN in a large Chinese cohort.Patients and Methods60 single nucleotide polymorphisms (SNPs) spanning a 400 kb range within FCGR gene locus were analyzed in 2100 DNA samples from patients with biopsy proven IgAN and healthy age- and sex-matched controls from the same population in Chinese.ResultsAmong the 60 SNPs investigated, 15 gene polymorphisms within FCGR gene locus (25%) were associated with susceptibility to IgAN. The most significantly associated SNPs within individual genes were FCGR2B rs12118043 (p = 8.74*10−3, OR 0.76, 95% CI 0.62–0.93), and FCRLB rs4657093 (p = 2.28*10−3, OR 0.77, 95% CI 0.65–0.91). Both conditional analysis and linkage disequilibrium analysis suggested they were independent signals associated with IgAN. Associations between FCGR2B rs12118043 and proteinuria (p = 3.65×10−2) as well as gross hematuria (p = 4.53×10−2), between FCRLB rs4657093 and levels of serum creatinine (p = 2.67×10−2) as well as eGFR (p = 5.41*10−3) were also observed. Electronic cis-expression quantative trait loci analysis supported their possible functional significance, with protective genotypes correlating lower gene expressions.ConclusionOur data from genetic associations and expression associations revealed potentially pathogenic roles of Fc receptor gene polymorphisms in IgAN.

Efficiency of immunoglobulin G replacement therapy in common variable immunodeficiency: correlations with clinical phenotype and polymorphism of the neonatal Fc receptor

Treatment of common variable immunodeficiency disorders (CVID) is based on replacement therapy using intravenous (i.v.) or subcutaneous (s.c.) immunoglobulin (Ig)G. Interindividual variation of IgG dose is common. A total of 380 CVID patients on stable IgG replacement from two prospective cohorts were analysed. An 'efficiency' index was defined as the ratio of serum IgG trough level minus IgG residual to the average weekly dose of IgG infusion. A reduced efficiency of IgG was associated independently with the i.v. route (P < 0·001) and with the presence of at least one CVID disease-related phenotype (lymphoproliferation, autoimmune cytopenia or enteropathy) (P < 0·001). High IgG efficiency was noted in patients homozygotes for the variable number tandem repeat (VNTR) 3/3 polymorphism of the neonatal Fc receptor gene [IgG Fc fragment receptor transporter alpha chain (FCGRT)] promoter, and this was particularly significant in patients treated with IVIG (P < 0.01). In a multivariate analysis, FCGRT VNTR 3/3 genotype (P = 0·008) and high serum albumin (P < 0·001) were associated independently with increased efficiency of i.v. Ig.

T-Cell Profiling Shows Marked Differences in Gene Expression Between Tumour Infiltrating (TIL) and Peripheral Blood (PB) Antibody-Bead Selected T-Cells From Fresh Lymph Node and PB Samples in Follicular Non-Hodgkin's Lymphoma (FL): Possible implications for Immunomodulatory Therapy

Abstract 683 Introduction:FL is one of the commonest B-cell lymphomas accounting for 25–30% of all newcases of non-Hodgkin’s lymphoma. Median survival ranges from 6–10 years with a constant annual rate of relapse and death. The cellular immune system through T-cells and macrophages/monocytes (MMs) has an important role in the response to therapy and long term remissions. Evidence for this stemmed from increased incidence and the poor response rates and survival in patients with inherited or acquired T-cell defects, and the graft-versus-leukaemia effect of allogeneic stem cell transplants. The number of tumour infiltrating lymphocytes (TILs) and MMs appear to predict clinical response and outcome in FL. A recent National Cancer Institute study looked at the prediction of survival in FL based on the molecular features of TILs with positive findings. However, this study used frozen material which could have changed the signatures, T-cells were not positively selected and would have been mixed with other non B-cells, negatively selected cells were stimulated with CD3 which could have changed the gene expression profile, the study looked only at the predictive value in relation to prognosis and did not look at PB T-cell (PBT)profile. Aims and methods:In the first stage reported here, we looked at positively selected TILs, PBT and MMs gene expression profile signatures in fresh lymph node samples (LNs) of histologically confirmed grades 1–3 FL in 14 patients and compared the profile results with similar cells positively selected from PB samples taken at the same time. The analysis was controlled with 4 histologically proven reactive hyperplasia LNs. Tissue samples were digested with a cocktail of enzymes, ficol separated and then positively selected for CD2, CD19, CD14 in that order using Dynabeads (Dynall) initially then Microbeads (Miltenyl Biotech) subsequently. CD2 was used to avoid T-cell receptor stimulation and change of expression with CD3. Some isolated T-cells were initially expanded in culture for purity assessment only by flow cytometry. T-cells and MMs were liquid nitrogen frozen in trisol whilst B-cells were stored in DMSO. RNA was extracted at the same time and analysed using Affymetrix Microarray Chips. Statistical analysis used 3 parameters to define significant change in expression: fold change of >1.5, p value of > 1×10−3and FDR of >0.5. Samples were analysed as paired and pooled as some cases did not yield adequate paired samples. Results:T-cell paired (10) samples showed 97 over (41) or under (56) expressed genes in TILs compared to PBT whilst pooled samples (14) showed 778 over (380) or under (398) expressed genes. The top over expressed genes (10 fold plus) using both methods of analysis were CXCL13 a B-cell chemotactic gene, IGJ which helps in assembling IgG and IgM, CTLA4 a regulatory molecule, CD200 which delivers an inhibitory signal for the macrophage lineage and several heat shock protein (HSP) genes. The top under-expressed genes (10 fold plus) include genes that regulate T-cell adhesion, migration and direct and indirect cytotoxicity such as a number of FC receptor genes needed for antibody dependant cell cytotoxicity, killer cell lectin-like receptor genes, fractalkine genes involved in the adhesion and migration of leukocytes, and granzyme, granulosin, lysosyme and other genes involved in T-cell cytotoxocity. MMs: Only pooled samples were analysed as the extracted cell numbers were too small to have paired analysis. Many more (3239) genes were over (1494) or under (1745) expressed in LN MMs compared to PB MMs. The top over expressed genes include genes that support B cell growth such as IGJ, BLNK and C4orf7, the B cell chemotactic gene CXCL13, signal transduction inhibitors and HSPs. The top underexpressed genes include those that regulate cell adhesion and survival, cell proliferation and migration and extracellular matrix assembly. Others include FC receptor, IL-1 and compliment genes necessary for cell cytotoxicity, and thrombomodulin genes. Conclusion:We believe this is novel data suggesting that TILs and tissue MMs appear to support B-cell growth in FL whilst inheriting several defects in direct and indirect cell cytotoxicity. Downregulating the significantly overexpressed and upregulating the under expressed genes through targeted therapy may provide the basis of non-chemotherapy immunomodulatory treatment of B-cell lymphomas. Disclosures:Rassam:BMS: Honoraria; Johnson and Johnson: Unrestricted research grant Other; ROCHE: Honoraria. Mufti:Celgene: Consultancy, Research Funding.

Tissues Expression, Polymorphisms Identification of FcRn Gene and Its Relationship with Serum Classical Swine Fever Virus Antibody Level in Pigs.

Neonatal Fc receptor (FcRn) gene encodes a receptor that binds the Fc region of monomeric immunoglobulin G (IgG) and is responsible for IgG transport and stabilization. In this report, the 8,900 bp porcine FcRn genomic DNA structure was identified and putative FcRn protein included 356 amino acids. Alignment and phylogenetic analysis of the porcine FcRn amino acid sequences with their homologies of other species showed high identity. Tissues expression of FcRn mRNA was detected by real time quantitative polymerase chain reaction (Q-PCR), the results revealed FcRn expressed widely in ten analyzed tissues. One single nucleotide polymorphism (SNP) (HQ026019:g.8526 C>T) in exon6 region of porcine FcRn gene was demonstrated by DNA sequencing analysis. A further analysis of SNP genotypes associated with serum Classical Swine Fever Virus antibody (anti-CSFV) concentration was performed in three pig populations including Large White, Landrace and Songliao Black pig (a Chinese indigenous breed). Our results of statistical analysis showed that the SNP had a highly significant association with the level of anti-CSFV antibody (At d 20; At d 35) in serum (p = 0.008; p = 0.0001). Investigation of expression and polymorphisms of the porcine FcRn gene will help us in further understanding the molecular basis of the antibody regulation pathway in the porcine immune response. All these results indicate that FcRn gene might be regarded as a molecular marker for genetic selection of anti-CSFV antibody level in pig disease resistance breeding programmes.