scholarly journals ROLES OF T AND B LYMPHOCYTES IN THE TERMINATION OF UNRESPONSIVENESS TO AUTOLOGOUS THYROGLOBULIN IN MICE

1974 ◽  
Vol 139 (3) ◽  
pp. 643-660 ◽  
Author(s):  
James A. Clagett ◽  
William O. Weigle
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
B Cells ◽  
B Lymphocytes ◽  
Bone Marrow Cells ◽  
Antigen Binding ◽  
Binding Studies ◽  
Normal Complement ◽  
Self Antigen

The data presented in this paper support the hypothesis that unresponsiveness to autologous thyroglobulin (Tg) exists in the T cells and responsiveness exists in the B cells. Such a conclusion is based on the results of antigen-binding studies where few, if any, thymocytes recognized syngeneic Tg. Comparable numbers of antigen-binding lymphocytes for syngeneic Tg were found in the spleens of normal intact mice and of nude mice. The latter fact suggested that B cells exist which recognize self-constituents. From antigen-suicide experiments, a clearer picture of the susceptibility of B cells to iodinated self-antigen and of the obligatory role of antibody in the induction of lesions was developed. Only bone marrow cells (B cells) were affected by [125I]syngeneic Tg, in which case the incidence of lesions was diminished. From adoptive transfer experiments, the results demonstrate that unresponsiveness may be terminated by immunization with a mixture of heterologous (cross-reacting) Tg's. In this situation T cells are required since a B-cell reconstituted host failed to make antibody (plaque-forming cells) and to develop lesions. T cells in this form of an unresponsive state may recognize determinants on the heterologous Tg unrelated to autologous Tg and as such stimulate the normal complement of B cells to produce antibody that both reacts with autologous and heterologous Tg.

Plasma and Intracellular Concentration of TNF and Its Receptors in Peripheral Blood and Bone Marrow in Different Stages of B-CLL.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4781-4781
Author(s):  
Jacek Rolinski ◽  
Agnieszka Bojarska-Junak ◽  
Iwona Hus ◽  
Anna Dmoszynska
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
B Cells ◽  
B Lymphocytes ◽  
Peripheral Blood ◽  
Biological Effects ◽  
Leukemic Cells ◽  
Control Group ◽  
Stage Of Disease ◽  
Positive Correlation

Abstract TNF has been proposed to play a role in the regulation of growth and death of leukemic B-CLL cells. However, the biological effects of TNF on leukemic cells, as well as its role as a prognostic factor need to be further investigated. The aim of the study was to eevaluate the correlation of TNF and its receptors in peripheral blood (PB) and bone marrow (BM) with the stage of B-CLL and some other clinical parameters. PB and BM were taken from 44 newly diagnosed, untreated B-CLL. patients. The control group consisted of 20 healthy subjects. We used flow cytometry technique to assess the capability of T and B lymphocytes to produce TNF and ELISA method to measure plasma levels of TNF and their soluble receptors. We found, that PB and BM plasma TNF concentration in the patients was significantly higher than in the healthy control (2.61 pg/ml. vs 0.62 pg/ml; and 2.91 pg/ml vs 0.75 pg/ml, respectively p<0.001). TNF concentration in PB and BM was significantly higher in Rai stage III–IV than in early stages (p<0.01). There was a correlation between the PB and BM TNF level and lymphocytosis (p<0.005) and the total tumor mass (TTM) (p<0.0001). The PB and BM TNF concentration positively correlated with the percentage of T CD3+ lymphocytes producing intracellular TNF (p<0.01). The percentage of T cells from PB an BM expressing cytoplasmic TNF was significantly higher in patients (PB:39.11±16.97%; BM:40.73±18.19%) than in normal controls (PB:15.74±7.95%; BM:18.80±12.93%) (p< 0.00001; p<0.005, respectively). In PB and BM from B-CLL patients the percentage of CD3+ cells expressing intracellular TNF was significantly higher than the percentage of CD19+/TNF+ cells (p<0.0001). Besides, it was found that the percentage of T cells expressing cytoplasmic TNF positively correlated with the stage of disease (p<0.01). In PB positive correlation were found between the number of T CD3+/TNF+ cells and lymphocytosis (p<0.05) and TTM (p<0.001). The percentage of leukaemic B cells positive for TNF did not correlate with the stage of disease. There was increased expression of TNF-RI and TNF-RII in leukaemic B cells in comparison to normal B-cells was observed (p<0.0001). We found positive correlation between the number of CD5+ B lymphocytes and the levels of soluble TNF-RII (sTNF-RII) (p< 0.05). The sTNF-RII levels in PB and BM significantly correlated with the stage of disease acc. Rai (p<0.0001). Furthermore, the sTNF-RII concentration positively correlated with lymphocytosis and TTM (p<0.0001). These results strongly support the key role TNF in B-CLL pathogenesis. Our results suggest that TNF may function as growth factor for B-CLL cells. CD3+T cells may be the important source of this cytokine in advanced B-CLL. It seems that changes in T cells capability to produce cytoplasmic TNF are associated with disease progression. However, further studies are required to confirm the key role of TNF in B-CLL pathogenesis.

Flow Cytometry Primary 10 Colours Panel for Chronic Lympho Proliferative Diseases Diagnosis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5190-5190
Author(s):  
Jonathan Brauner ◽  
Ingrid Beukinga ◽  
Zoulikha Amraoui ◽  
Zaina Kassengera ◽  
Michel Toungouz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Lymphocytes ◽  
Plasma Cells ◽  
Cell Lymphoma ◽  
Cd10 Expression ◽  
Complete Characterisation

Abstract Abstract 5190 Objectives: Definition of the primary antibodies panel for 10 colours flow cytometry able to describe normal and clonal T, B lymphocytes and plamocytes in blood and bone marrow. Once clonalities are detected, the complete characterisation of Chronic Lymphoproliferative Diseases (CLPD) is supported by secondary panels chosen based on the results of CD5/CD10 expression for clonal B lymphocytes, CD27/CD38 for plasmatocytes and CD3/CD27 for clonal T cells. Materials and Methods: Blood and bone marrow of patients (N=50) with CLPD (mainly B-CLL). Samples are enumerated by haematology analyzer DxH 800 then 106 cells are washed three times, stained with the antibodies combination and red blood cells lysed with Versalyse (TM. Beckman Coulter). The samples were analysed on a 10 colours Navios flow cytometer (Beckman Coulter Fullerton, CA). The staining panel consists of 14 antibodies (CD45, CD8, CD4, CD5, CD3, CD19, CD38, λ, κ, CD23, CD5, CD10, CD14, CD27) conjugated with 10 different fluorochromes. The fixed gating strategy allows linking Navios analysis software to the middleware Remisol which drives the choice of the secondary panel. In some cases a third tube is performed for Ki67 or Zap-70 intra-cytoplasmic staining. Results: Monocytes are removed on the basis of their CD14/CD4 expression. B lymphocytes are CD19 positive. Normal naïve/memory B cells, hematogones and plasma cells are defined by their CD27, CD10 and CD38 expression. Eventual monoclonality is sought by analysis of the distribution of Kappa and Lambda light chains. A first classification of B cell lymphoma is achieved with the CD5 and CD10 expression of the clone (CD5+/CD10−: B-CLL MCL and few MZL, CD5−/CD10−: MZL and related, CD5−/CD10+ DLBCL and FL). Analysis of CD27, CD20 and CD23 expression allows discriminating between CD5+/CD10- lymphomas. All the 50 samples were correctly detected as CLPD and the automated Remisol choice of the second panel fit to the final diagnosis of all the cases of this small series. T lymphocytes are defined by their CD3 and CD5 expression. The analysis of CD4/CD8 balance and CD27/CD5 distribution are first line test when T cell clonality is suspected. There is a special gating to detect CD3-CD4+ T cell lymphoma and double negativity of CD4 and CD8 is a surrogate marker for gamma/delta T cells. NK cells are mentioned as not-T not-B lymphocytes, without specific staining. Conclusion/Discussion:This 10 colours 14 antibodies panel allows describing in one tube normal T and B cells, hematogones, memory and naives B cells plasma cells and detects T and B clonalities. This panel follows a similar logic than the Euroflow LST tube but with 10 colours and with Beckman Coulter's technology and antibodies. Moreover, this combination helps discriminating rapidly the CD5+/CD10- lymphomas while the complete characterisation of CD5 negative lymphomas only require less than 6 antibodies second tube. This is a paperless (all the process is driven and controlled by Remisol), fast and inexpensive diagnostic approach (always less than 20 antibodies required). Disclosures: Pradier: Beckman Coulter: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals The bcl-2 gene product inhibits clonal deletion of self-reactive B lymphocytes in the periphery but not in the bone marrow.

1993 ◽  
Vol 178 (4) ◽  
pp. 1247-1254 ◽  
Author(s):  
S Nisitani ◽  
T Tsubata ◽  
M Murakami ◽  
M Okamoto ◽  
T Honjo
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
Transgenic Mice ◽  
Gene Product ◽  
B Lymphocytes ◽  
Immunoglobulin Genes ◽  
Clonal Deletion ◽  
Immature B Cells ◽  
B1 Cells ◽  
Self Antigen

To test whether the product of the bcl-2 proto-oncogene blocks clonal deletion of self-reactive B cells, we have generated transgenic mice carrying the bcl-2 gene and the immunoglobulin genes for the anti-erythrocyte 4C8 antibody. In these transgenic mice, clonal deletion of self-reactive immature B cells in the bone marrow was not inhibited in spite of expression of the bcl-2 gene. In contrast, self-antigen-induced clonal deletion of mature self-reactive Ly-1 B (B1) cells in the peritoneal cavity was inhibited in the transgenic mice. These results indicate that the mechanism for clonal deletion of immature self-reactive B cells in the bone marrow differs from that of mature self-reactive B cells in the periphery.

In Vitro expanded STAT1−/− Regulatory T Cells Prevent Acute Graft Versus Host Disease (GVHD) and Promote Donor Cell Engraftment In Allogeneic Fully MHC-Mismatched Bone Marrow Transplant

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 732-732
Author(s):  
Huihui Ma ◽  
Caisheng Lu ◽  
Judy Ziegler ◽  
Suzanne Lentzsch ◽  
Markus Y Mapara
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Cells ◽  
Donor Cell ◽  
Treg Cells ◽  
Cell Engraftment ◽  
Lethal Irradiation

Abstract Abstract 732 Treg cells have been recognized as critical regulators of the immune response and shown to prevent the development of GVHD. However, little is known about of the role of STAT1 signaling in Treg cells during the development of GVHD. In this study, we tried to investigate how STAT1 signaling controls donor Treg development and function in the setting of GVHD. For this purpose we studied the role of STAT1 in natural and inducible Treg (nTreg and iTreg, respectively). To better understand the influence of STAT1-deficiency on the proliferation of nTreg cells, purified splenic STAT1−/− or STAT1+/+ CD4+CD25+ cells were labeled with Carboxyfluorescein succinimidyl ester (CFSE) and cultured on anti-CD3 coated plates in the presence of anti-CD28 and IL-2 for 3 days and analyzed for proliferation and viability. After 72h of in vitro culture 50% of the STAT1+/+ starting population were no longer viable compared to only 10% of STAT1−/− cells. Furthermore, we noted a significantly increased expansion of STAT1-deficient CD4+CD25+Foxp3+ Treg cells compared to STAT1+/+ Treg cells (p<0.001). In line with these findings, STAT1-deficiency resulted in a significantly higher proportion of CFSElo cells indicating vigorous proliferation (85% Foxp3+CFSElo in STAT1−/− compared to only 65% Foxp3+CFSElo in STAT1+/+ Treg cells. Furthermore, at the end of the culture 30% of the STAT1+/+ CD4+CD25+ population were Foxp3-negative compared to only 10% of the STAT1−/− cells. We next determined the impact of STAT1 on the generation of iTreg cells in vitro. For this purpose CD4+CD25− cells from STAT1−/− or STAT1+/+ mice were cultured for 3 days on anti-CD3 coated plates in the presence of anti-CD28 antibodies, hTGF-β, mIL-2, anti-IFN-γ and anti-IL-4 for 3 days. Compared to STAT1+/+, we observed significantly enhanced generation of iTregs from STAT1−/− splenocytes (19.9%±3.0% vs. 10.6%±1.3%, p=0.008). We then performed studies to assess the in vivo generation of iTreg. For that purpose BALB/c mice were reconstituted with T Cell Depleted (TCD) 129.STAT1+/+Bone Marrow Cells (BMC) following lethal irradiation and recipients were co-injected with CD4+CD25− cells purified from either 129.STAT1+/+ or 129.STAT1−/− splenocytes. We again noted a significantly higher proportion of CD4+CD25+ Foxp3+ cells in recipients of CD4+CD25−STAT1−/− cells compared to recipients of STAT1+/+ T cells indicating a significantly increased conversion of CD4+CD25- cells into Treg cells. To confirm the in vitro results we tested the functional ability of in vitro expanded (using anti-CD3, anti-CD28, IL-2 and TGF-β) STAT1+/+ or STAT1−/− Treg cells to block induction of GVHD. GVHD was induced in BALB/c mice following lethal irradiation (800rad) and fully MHC-mismatched BMT using 129.STAT1+/+ bone marrow cells plus 129.STAT+/+ conventional T cells (Tcon). Animals were co-injected with expanded Treg cells from either 129.STAT1+/+ or 129.STAT1−/− donors at a ratio of 1:1 or 1:4 (Treg:Tcon). STAT1−/− or STAT1+/+ Treg cells were equipotent in completely preventing GVHD mortality. However, compared to recipients of STAT1+/+ Treg recipients of STAT1−/− Treg showed reduced signs of GVHD morbidity as determined by a significantly improved weight development. Furthermore, recipients of STAT1−/− Treg showed significantly increased donor cell engraftment compared to recipients of STAT1+/+Treg (donor CD4+ [87% vs. 60%, p=0.03], CD8+[99% vs. 96%, p=0.04], Mac1+[96% vs. 77%, p=0.02] and B220+[100% vs. 96%, p=0.007]) cells in the recipient spleen. These observations clearly demonstrate that STAT1 is a critical regulator of Treg cell development and expansion and that targeting STAT1 in CD4+ T cells may facilitate in vitro and in vivo generation/expansion of Treg cells for therapeutic use in GVHD while also promoting donor cell engraftment. Disclosures: Lentzsch: Celgene Corp: Research Funding. Mapara:Resolvyx: Research Funding; Gentium: stocks.

scholarly journals T-Lymphocyte precursors. I. Synergy between precursor and mature T lymphocytes in the response to concanavalin A.

1976 ◽  
Vol 144 (2) ◽  
pp. 456-466 ◽  
Author(s):  
J J Cohen ◽  
S S Fairchild
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Concanavalin A ◽  
Bone Marrow Cells ◽  
Mouse Bone Marrow ◽  
Synergistic Activity ◽  
Preincubation Medium

When mouse bone marrow cells are mixed with cortisol-resistant thymocytes and stimulated in vitro with concanavalin A, the mitogenic response observed is much greater than additive, that is, it is synergistic. Between 94 and 96% of responding cells could be identified as T cells (Thy-1 positive) and of these, 79-100% derived from the cortisol-resistant thymocyte population, not from the bone marrow. Purified macrophages could not replace bone marrow; and marrow depleted of mature T or B cells worked as well as normal marrow. Thus, T and B cells and macrophages were ruled out as the synergizing cell of bone marrow. Nude spleen contained 10 times as many precursors of T cells as did nude marrow and was 10 times better at synergy with cortisol-resistant thymocytes. This implication of the pre-T cell as synergizer was supported by the finding that the synergistic activity of marrow was lost on preincubation, but maintained if the preincubation medium contained thymosin or cyclic AMP. Thus, the ability to enhance the response of relatively mature T cells to Con A is a property of pre-T cells. It is anticipated that this property will allow more detailed studies of T-cell precursor development in mice, and possibly in man.

Human donor bone marrow cells induce in vitro “suppressor T cells” that functionally suppress autologous B cells

2003 ◽  
Vol 64 (1) ◽  
pp. 21-30 ◽  
Author(s):  
Manuel R Carreno ◽  
Laphalle Fuller ◽  
James M Mathew ◽  
Gaetano Ciancio ◽  
George W Burke ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
B Cells ◽  
Bone Marrow Cells ◽  
Suppressor T Cells ◽  
Human Donor ◽  
Donor Bone Marrow ◽  
Marrow Cells

scholarly journals Activated Murine B Lymphocytes and Dendritic Cells Produce a Novel CC Chemokine which Acts Selectively on Activated T Cells

1998 ◽  
Vol 188 (3) ◽  
pp. 451-463 ◽  
Author(s):  
Christoph Schaniel ◽  
Evangelia Pardali ◽  
Federica Sallusto ◽  
Mattheos Speletas ◽  
Christiane Ruedl ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Dendritic Cells ◽  
Lymph Node ◽  
Amino Acid ◽  
B Cells ◽  
B Lymphocytes ◽  
Open Reading Frame ◽  
Reading Frame ◽  
Splenic Cells

Genes were isolated using the suppression subtractive hybridization method by stimulation of pro/pre B cells with anti-CD40 and interleukin (IL)-4 to mature Sμ-Sε–switched cells. One of the strongly upregulated genes encodes a novel murine CC chemokine we have named ABCD-1. The ABCD-1 gene has three exons separated by 1.2- and 2.7-kb introns. It gives rise to a 2.2-kb transcript containing an open reading frame of 276 nucleotides. Two polyadenylation sites are used, giving rise to cDNAs with either 1550 or 1850 bp of 3′ untranslated regions. The open reading frame encodes a 24 amino acid–long leader peptide and a 68 amino acid–long mature protein with a predicted molecular mass of 7.8 kD. ABCD-1 mRNA is found in highest quantities in activated splenic B lymphocytes and dendritic cells. Little chemokine mRNA is present in lung, in unstimulated splenic cells, in thymocytes, and in lymph node cells. No ABCD-1 mRNA is detected in bone marrow, liver, kidney, or brain, in peritoneal exudate cells as well as in the majority of all unstimulated B lineage cells tested. It is also undetectable in Concanavalin A–activated/IL-2–restimulated splenic T cells, and in bone marrow–derived IL-2–induced natural killer cells and IL-3–activated macrophages. Recombinant ABCD-1 revealed a concentration-dependent and specific migration of activated splenic T lymphoblasts in chemotaxis assays. FACS® analyses of migrated cells showed no preferential difference in migration of CD4+ versus CD8+ T cell blasts. Murine as well as human T cells responded to ABCD-1. Freshly isolated cells from bone marrow, thymus, spleen, and lymph node, IL-2–activated NK cells, and LPS-stimulated splenic cells, all did not show any chemotactic response. Thus, ABCD-1 is the first chemokine produced in large amounts by activated B cells and acting selectively on activated T lymphocytes. Therefore, ABCD-1 is expected to play an important role in the collaboration of dendritic cells and B lymphocytes with T cells in immune responses.

scholarly journals Collaboration of histoincompatible T and B lymphocytes using cells from tetraparental bone marrow chimeras.

1975 ◽  
Vol 142 (4) ◽  
pp. 989-997 ◽  
Author(s):  
H von Boehmer ◽  
L Hudson ◽  
J Sprent
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Parental Strain ◽  
Secondary Response ◽  
Cell Populations ◽  
Sheep Erythrocytes ◽  
Bone Marrow Chimeras

T-B collaboration has been studied in a secondary response to sheep erythrocytes using either syngeneic or allogeneic T- and B-cell combinations. T cells prepared from tetraparental bone marrow chimeras (TBMC), carrying H-2 determinants of one parental strain only, cooperated with syngeneic, as well as with allogeneic B cells carrying the alloantigens to which the T cells had been tolerized in the chimeric environment. When TBMC-derived cells of a single H-2 specificity were transferred with a mixture of TBMC-derived B cells of both H-2 types of the parental strains, no preference for syngeneic cooperation was found. The data therefore suggest that the presence of differing H-2-complex determinants on the allogeneic T- and B-cell populations of the two different strain combinations tested do not interfere with T-B collaboration when the cell populations studied are mutually tolerant.

scholarly journals The Complex Role of KDM6A in B-Cell Development and Function

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 513-513
Author(s):  
Ling Tian ◽  
Monique Chavez ◽  
Lukas D Wartman
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
B Cells ◽  
B Cell ◽  
Bone Marrow Cells ◽  
Cell Development ◽  
Young Female ◽  
B Cell Development ◽  
And Function

Abstract Loss-of-function mutations in KDM6A, an X-linked H3K27 demethylase, occur recurrently in B-cell lymphoid malignancies, including B-cell acute lymphoblastic leukemia and non-Hodgkin lymphoma. Germline inactivating mutations in KDM6A cause a neurodevelopmental disorder called Kabuki syndrome that is associated with recurrent infections and hypogammaglobulinemia.1 The role of KDM6A in normal B-cell development and function, as well as how the somatic loss of KDM6A contributes to B-cell malignancies, has not been completely defined. To address this issue, we generated a conditional knockout mouse of the KDM6A gene (with LoxP sites flanking the 3rd exon) and crossed these mice with Vav1-Cre transgenic mice to selectively inactivate KDM6A in hematopoietic stem/progenitor cells. We characterized normal hematopoiesis from young (6 to 8 week old) and aged (50 to 55 week old) male and female KDM6A conditional KO mice. We found a significant shift from lymphoid to myeloid differentiation in the bone marrow and peripheral blood of these mice. Young, female KDM6A-null mice had mild splenomegaly. Their spleens had an increased number of neutrophils (Gr-1+CD11b+ cells) and erythrocyte progenitors (CD71+Ter119+ cells) and a decreased number of B-cells (B220+ cells). These changes became more pronounced with age and were specific to the female, homozygous KDM6A knockout mice. Furthermore, analysis of B-cell maturation showed that the loss of KDM6A was associated with decreased immature (B220+IgM+ cells) and mature, resting B-cells (B220+IgD+ cells) in the spleen. Similar changes were present in the bone marrow (decreased B220+IgM+ cells and B220+CD19+ cells) and peripheral blood (decreased B220+IgM+, B220+IgD+ and B220+CD19+ cells). Early B-cell development is also altered in KDM6A-null mice. Flow cytometry showed a decrease in multipotent progenitor cells (MPPs) with a decrease in both common lymphoid progenitors (CLPs) and B cell-biased lymphoid progenitors (BLPs) in young, female KDM6A-null mice bone marrow. Next, we performed flow cytometry to catergorize the Hardy fractions of early B-cell development on bone marrow isolated from young, female KDM6A-null mice. B-cell progenitor analysis (Hardy profiles) showed an increase in Fraction A with a concomitant decrease in Fraction B/C and Fraction D, which was likely indicative of an incomplete block in B-cell differentiation after the Fraction A stage. When bulk bone marrow cells isolated from young, female KDM6A-null mice were plated in methylcellulose supplemented with interleukin-7, we observed a significantly decreased colony formation compared with bone marrow cells isolated from wildtype littermates. This pre-B lymphoid progenitor cell plating phenotype was expected given the flow cytometry results of decreased B-cell progenitors outlined above. We examined the effect of the loss of KDM6A expression on germinal center (GC) formation in the spleen following immunization with NP-CGG (4-Hydroxy-3-nitrophenylacetyl-Chicken Gamma Globulin, Ratio 16). Two weeks after NP-CGG immunization, we observed a significant decrease in follicular B-cells (FO) and a significant increase in GC B-cells as compared to wildtype littermates (Figure 1). The result is significant as GC B-cells are thought to be the cell-of-origin of follicular and DLBCL. To determine if inactivation of KDM6A affected antibody production, we measured IgM, IgG, IgE and IgA levels by ELISA from serum isolated from young, female KDM6A-null mice. Results revealed higher levels of IgM and lower levels of IgG in serum from KDM6A-null mice, which is suggestive of a class switch recombination (CSR) defect. Concordant with this result, we observed that the loss of KDM6A impaired CSR to IgG1 in splenic B cells after in vitro stimulation for three days with lipopolysaccharide (LPS), an anti-CD180 antibody and interleukin-4. Moreover, we observed a striking defect in the production of plasma cells from KDM6A-null B-cells after LPS stimulation. Taken together, our data shows that KDM6A plays an important, but complex, role in B-cell development and that loss of KDM6A impedes the B-cell immune response in a specific manner that may contribute to infection and B-cell malignancies.Stagi S, et al. Epigenetic control of the immune system: a lesson from Kabuki syndrome. Immunol Res. 2016; 64(2):345-359. Disclosures No relevant conflicts of interest to declare.

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