Abstract 81: B Lymphocytes Trigger MCP3-Dependent Mobilization of Monocytes and Promote Adverse Ventricular Remodeling After Myocardial Infarction

Leukocyte infiltration in ischemic areas is a hallmark of myocardial infarction, and persistent infiltration of innate immune cells, such as neutrophils and Ly6Chi monocytes, has been shown to promote adverse cardiac tissue remodeling. However, little is known regarding the role of mature B lymphocytes, which play a crucial role in the activation of the inflammatory response in several immune-mediated diseases. Here, we hypothesized that B lymphocytes might modulate the inflammatory response and affect the immune-dependent adverse cardiac remodeling. In a mouse model of myocardial infarction, cardiac B lymphocytes levels peaked at day 5 after the onset of infarction. Of interest, treatment with a CD20-specific monoclonal antibody decreased circulating and infiltrating B cell numbers (p=0.0008 and p=0.0002 vs control), reduced infarct size and post-ischemic immunoinflammatory response, and improved cardiac function (p=0.02 vs control) assessed by echocardiography. Intriguingly, B cell depletion was associated with an impairment of Ly6Chi monocytes mobilization from bone marrow (p=0.02 vs control), leading to reduced levels of circulating and infiltrating cardiac monocytes. The acute infarction led to transient increase of both MCP-1 and MCP-3 levels. Interestingly, B cell depletion was associated with a significant and selective reduction of MCP-3 (p=0.03 vs control) but did not alter MCP-1 levels (p=0.11). Cultured activated B cells released MCP-3 and treatment with a neutralizing MCP-3 antibody abrogated B lymphocytes-induced migration of cultured monocytes. Finally, transfer of B cell-depleted splenocytes into Rag1 -/- mice improved cardiac function after myocardial infarction compared to the transfer of non-depleted splenocytes (p=0.005). This effect was abrogated after re-supplementation with B lymphocytes isolated from wild-type mice (p=0.0007) but not from MCP-3-deficient animals (p=0.7008). In conclusion, we show that following acute myocardial infarction, B lymphocytes, trigger an MCP-3-dependent mobilization of Ly6Chi monocytes from the bone marrow to the blood, leading to their recruitment into the injured myocardium and to exacerbation of tissue inflammation, thereby promoting adverse cardiac remodeling.

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P6598MicroRNA 21 and Hypoxia Inducible Factor 1 synchronize the impact of B lymphocytes on cardiac function after acute myocardial infarction

European Heart Journal ◽

10.1093/eurheartj/ehz746.1186 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

Y Sun ◽

C Pinto ◽

X Loyer ◽

V Duval ◽

P Alayrac ◽

...

Keyword(s):

Myocardial Infarction ◽

Bone Marrow ◽

B Cells ◽

Cardiac Function ◽

B Cell ◽

B Lymphocytes ◽

Cardiac Repair ◽

Acute Mi ◽

The Impact ◽

Deficient Mice

Abstract Background Myocardial infarction (MI) is a severe ischemic disease responsible for heart failure and sudden death. Mature B lymphocytes have been shown to exacerbate tissue injury and deterioration of cardiac function after MI. However, the cellular and molecular mechanisms governing B cell deleterious effects in the ischemic milieu remain to be defined. Purpose In this study, we speculate that endogenous activation of the miR21/HIFα-related pathways mediates the effect of B lymphocytes on post-ischemic cardiac remodeling. Methods Acute MI was induced by permanent ligation of the left anterior descending artery in mice. Cardiac function and remodeling was determined by echocardiography and immunohistochemistry. Inflammatory cell number and phenotype were defined by FACS analysis. To evaluate the role of HIFα isoforms in B cells, we generated mice with B cell lineage specific (Cd79aCre/+) conditional deletion of HIF1α (HIF1αflox/flox), HIF2α (HIF2αflox/flox), or both isoforms (HIF1α-HIF2αflox/flox). Results Acute MI increased miR21 levels in B cells. miR21 deficient mice showed reduced B cell numbers in the spleen, blood and subsequently in the injured cardiac tissue. Transplantation of bone marrow derived cells isolated from miR21-deficient mice (miR21−/−) improved cardiac function and remodeling when compared to administration of wild-type (WT) bone marrow cells. Similarly, in Rag1−/− immunodeficient mice with acute MI, re-supplementation with miR21−/− B lymphocytes restored cardiac repair and function when compared to injection of WT B cells. miR21 abrogated PTEN contents and subsequently enhanced HIF1α levels in cultured B cells. B cell deletion of HIF1α, but not that of HIF2α, reduced B cell accumulation and improved cardiac function after MI. Mice, which were equally deficient in HIF1α and HIF2α, also exhibited abrogation of adverse ventricular remodeling and showed recovery of cardiac function after MI. Toll like receptor agonist, CpG, fostered the release of the monocyte chemo-attractant protein, Ccl7, in cultured WT B cells but not in miR21- or HIF1α- deficient B cells. Ccl7 circulating levels were also reduced in miR21−/− and Cd79aCre/+/HIF1α flox/flox animals after acute MI. Ccl7 down-regulation hampered Ly6Chigh monocyte infiltration in the ischemic myocardium, leading to decreased infarct size and interstitial fibrosis, supporting cardiac repair. Conclusion This work reveals a novel function for miR21/HIF1α related pathways in B lymphocyte dependent effect on cardiac function and remodeling in the setting of acute MI.

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B Cell Depletion and Signs of Sepsis Acquired Immunodeficiency in Bone Marrow and Spleen of COVID-19 Deceased

International Journal of Infectious Diseases ◽

10.1016/j.ijid.2020.12.078 ◽

2021 ◽

Author(s):

Jana Ihlow ◽

Edward Michaelis ◽

Selina Greuel ◽

Verena Heynol ◽

Annika Lehmann ◽

...

Keyword(s):

Bone Marrow ◽

B Cell ◽

Cell Depletion ◽

B Cell Depletion ◽

Acquired Immunodeficiency

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Autoantibody Production during Chronic Graft-Versus-Host Disease Does Not Associate with Long-Term Persistence of Host B Cells in Humans

Blood ◽

10.1182/blood.v112.11.1180.1180 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1180-1180

Author(s):

Simona Piemontese ◽

Zulma Magnani ◽

Jacopo Peccatori ◽

Claudio Bordignon ◽

Chiara Bonini ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

B Lymphocytes ◽

Graft Versus Host Disease ◽

Cell Depletion ◽

B Cell Depletion ◽

Autoantibody Production ◽

Graft Versus Host

Abstract Background. Chronic graft-versus-host disease (cGvHD) is a common complication of allogeneic hemopoietic cell transplantation (allo-HCT). The pathogenesis of cGvHD is poorly understood. In cGvHD, the homeostasis of B lymphocytes is perturbed, as demonstrated by the production of autoantibodies. B-cell depletion with monoclonal antibodies (mAb) interferes with autoantibody production and ameliorates signs and symptoms of cGvHD. In mouse models, cGvHD and autoantibodies associate with the long-term persistence of host B cells after allo-HCT (Sylvain Perruche et al., Transplantation 2006). It has been postulated that host B cells may present alloantigens to donor T cells and, in turn, receive help for autoantibody production. This could be crucial to the pathogenesis of cGvHD. Aim. To investigate whether the long-term persistence of host B lymphocytes is associated with cGvHD and autoantibodies in humans. Patients and methods. We recruited 13 consecutive patients with active cGvHD (4 mild, 5 moderate, 4 severe according to NIH classification) with a median time of onset of 6 months (range 3–36) from HLA-identical sibling (9 patients) and HLA-matched unrelated (4) allo-HCT. As controls, we chose 10 patients that underwent HLAidentical sibling (2), HLA-matched unrelated (5) or haploidentical (3) allo-HCT and never experienced cGvHD. In the two groups, we studied: circulating autoantibodies, including anti-nuclear (ANA), anti-DNA, anti-extractable nuclear antigen, anti-beta2 glycoprotein, anti-neutrophil cytoplasm, anti-thyroid, anti-mytocondria antibodies, rheumatoid factor, absolute numbers of T (CD3+, CD4+, CD8+), conventional B (CD19+), B1 (CD5+/CD19+) and NK cells (CD16+/CD56+) in the graft and in the peripheral blood, microchimerism by short-tandem repeats (STR) on B, T and myeloid cells purified by immunomagnetic cell sorting (sensitivity 0,01%). Results. Patients with cGvHD had high-titer circulating ANA (>1:160) more frequently than controls (54% versus 10%, P<0,05). All other autoantibodies were negative. Peripheral T-cell counts were lower in patients with cGvHD than in controls (for CD8+ cells P<0,05). This was not due to a difference in the absolute numbers of T lymphocytes within the graft between the two groups. Peripheral counts of conventional B and B1 cells in patients with cGvHD were similar to controls. Autoantibodies and cGvHD were not associated with the persistence of host B lymphocytes, since the analysis of STR on purified B cells revealed that they were all of donor origin. T and myeloid cells were also of donor origin. Of interest, in univariate analysis, in vivo B-cell depletion with mAb for the prophylaxis against Epstein-Barr virus-related lymphoproliferative disease showed a trend towards a lower risk of cGvHD (P=0,06). Conclusions. This study indicates that autoantibody production during cGvHD does not associate with long-term persistence of host B cells in humans. Moreover, it suggests that the early depletion of donor B lymphocytes in vivo may be effective for GvHD prophylaxis

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A unique population of IgG-expressing plasma cells lacking CD19 is enriched in human bone marrow

Blood ◽

10.1182/blood-2014-02-555169 ◽

2015 ◽

Vol 125 (11) ◽

pp. 1739-1748 ◽

Cited By ~ 83

Author(s):

Henrik E. Mei ◽

Ina Wirries ◽

Daniela Frölich ◽

Mikael Brisslert ◽

Claudia Giesecke ◽

...

Keyword(s):

Bone Marrow ◽

Immune Responses ◽

B Cell ◽

Plasma Cells ◽

Human Bone ◽

Human Bone Marrow ◽

Cell Depletion ◽

B Cell Depletion ◽

Healthy Human ◽

Key Points

Key Points Healthy human BM is enriched for PC lacking CD19 that express a prosurvival and distinctly mature phenotype. CD19− PC resist mobilization into blood during immune responses after vaccination as well as B-cell depletion with rituximab.

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Diacerein Improves Left Ventricular Remodeling and Cardiac Function by Reducing the Inflammatory Response after Myocardial Infarction

PLoS ONE ◽

10.1371/journal.pone.0121842 ◽

2015 ◽

Vol 10 (3) ◽

pp. e0121842 ◽

Cited By ~ 15

Author(s):

Anali Galluce Torina ◽

Karla Reichert ◽

Fany Lima ◽

Karlos Alexandre de Souza Vilarinho ◽

Pedro Paulo Martins de Oliveira ◽

...

Keyword(s):

Myocardial Infarction ◽

Inflammatory Response ◽

Cardiac Function ◽

Ventricular Remodeling ◽

Left Ventricular Remodeling ◽

Left Ventricular

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Virus infection-associated bone marrow B cell depletion and impairment of humoral immunity to heterologous infection mediated by TNF-?/LT?

European Journal of Immunology ◽

10.1002/eji.200425597 ◽

2005 ◽

Vol 35 (2) ◽

pp. 524-532 ◽

Cited By ~ 12

Author(s):

Persephone Borrow ◽

Sam Hou ◽

Simone Gloster ◽

Miranda Ashton ◽

Lisa Hyland

Keyword(s):

Bone Marrow ◽

Virus Infection ◽

B Cell ◽

Humoral Immunity ◽

Cell Depletion ◽

B Cell Depletion

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Rituximab Mediated Depletion of B Cells Following Transplant of Human CD20 Transgenic Mouse Bone Marrow Results in Prolonged B Cell Depletion and Augmented Anti-Tumor Immune Response.

Blood ◽

10.1182/blood.v106.11.2205.2205 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2205-2205

Author(s):

Yu D. Zhang ◽

Hovav Nechushtan ◽

Monica Jones ◽

Andrew Chan ◽

Seung-uon Shin ◽

...

Keyword(s):

Bone Marrow ◽

T Cells ◽

B Cells ◽

B Cell ◽

Transgenic Mouse ◽

Treated Group ◽

Cell Depletion ◽

Mouse Bone Marrow ◽

B Cell Depletion ◽

Post Transplant

Abstract We previously demonstrated rejection of murine tumors due to enhanced anti-tumor cytolytic and Th1 cytokine responses in mice lacking B cells (BCDM) compared to immunocompetent mice. We wished to compare immune and anti-tumor responses in BCDM to mice functionally depleted of B cells using an anti-human CD20 antibody (Rituximab). We evaluated Rituximab effects on the outgrowth of human CD20 transgenic mouse (huCD20 Tg) B cells following the transplant of huCD20Tg CD45.2+ bone marrow (BM) into sublethally irradiated congenic CD45.1+ mice. CD45.1 mice were irradiated with 9.5Gy at day -1, followed by infusion of 3x106 huCD20Tg BM cells on day 0, and by treatment with or without Rituximab at 400ug/mouse given once weekly i.v. for 4 weeks. Without Rituximab treatment, B cell percentages in the peripheral blood (PB) were approximately 46.4%±1.3; spleen, 77.8%±1.5; and peripheral lymph nodes (pLNs), 43%±1.5 at day 47. With Rituximab treatment, CD19+ cells in the PB, spleen and pLNs were 1.8%±0.4, 4.3%±1.3, and 0.8%±0.2 respectively at 47days post transplant. Higher percentages of CD3+ T cells in PB, spleen and pLNs (66.1%±0.5, 51.7%±1.1 and 43.0%±3.8) were noted in the Rituximab treated group compared to controls (19%±0.9, 10.3%±1.0 and 32.3%±1.7 respectively). The percentage of remaining B cells in PB declined progressively from 5.6% at day 13 to 1.8% at day 47 post transplant indicating that Rituximab depletion of huCD20+ transgenic B cells was progressive, durable and very effective. In contrast, CD3+ cells in PB increased from 11.2% (day 13) to 66.1 % (day 47) following Rituximab treatment. Interestingly reconstitution with endogenous murine B cells in huCD20 transplanted mice was minimal. The huCD20 Tg donor-derived T cells in the Rituximab treated group maintained a CD44low naive phenotype. The growth of MC38 tumors implanted 15 days following transplant was significantly slowed in the Rituximab treated group. Increased IFN-γ production and higher expression of the cytolytic marker CD107a by T cells was seen in the Rituximab treated group compared to controls. The combination of myeloablative irradiation, huCD20 transgenic bone marrow transfer and Rituximab depletion, was able to generate mice devoid of CD20+ B cells. Rituximab treated huCD20+ reconstituted B cell depleted mice have substantially higher percentages of T cells than control non-Rituximab treated mice, show sustained depression of B cell numbers and manifest an increased anti-tumor Th1 response. The huCD20 transplant model will be useful in studying effects of post-transplant B cell depletion on immune reconstitution and in the design of future clinical transplant and immunization strategies.

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Selective Rapid B-Cell Depletion In Vivo by Pharmacologic IKK2 Inhibition.

Blood ◽

10.1182/blood.v104.11.2481.2481 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2481-2481

Author(s):

Christopher C. Fraser ◽

Kumiko Nagashima ◽

Vito Sasseville ◽

Jim Deeds ◽

Alice McDonald ◽

...

Keyword(s):

Bone Marrow ◽

B Cells ◽

Oral Dose ◽

B Cell ◽

Single Oral Dose ◽

Colony Growth ◽

B Cell Development ◽

Cell Depletion ◽

B Cell Depletion

Abstract Studies using genetically deficient mice have revealed that members of the NF-kB family play key roles in B-cell development. IKK2 which activates NF-kB by targeting degradation of IkB, is also required for B-cell development. We have studied the role of IKK2 in hematopoiesis using a chemical specific inhibitor (ML120B). Mice given daily oral dosing of ML120B for 4 days had severe B-cell depletion in spleen and bone marrow. B-cells at all stages (pro-B, pre-B, immature and mature B) were depleted 10 fold in the bone marrow while granulocyte numbers were largely unaffected. IKK2 inhibition in vivo showed selective sensitivity of B-cell progenitors (4 fold decrease) in the marrow compared to myeloid progenitors which were unaffected at an equivalent dose. Foci of cells with an apoptotic morphology were visible in bone marrow and spleen within 6 hours of a single oral dose. Apoptotic cells detected by labeling fragmented DNA were increased within splenic follicles (6 fold) and bone marrow. Also an increase in B220+ / annexin V+ cells and a decrease in pre-B (B220+/IgM−) cells in the marrow were observed. RNA expression studies in the marrow 6 hours after a single oral dose revealed a decrease in IL-7 and increased GM-CSF expression. Image analysis of B220 in spleens within 18 hours of a single dose of an IKK inhibitor revealed decreased follicle size. In order to evaluate hematopoietic progenitor sensitivity to NF-kB inhibition, dose responses to ML120B, panepoxydone (PPD) and proteasome inhibitor Lactacystin (Lcyst) were evaluated in B-cell and myeloid bone marrow colony assays. Inhibitors PPD and Lcyst were more effective at inhibiting B-cell colony growth than myeloid colony growth. In summary, pharmacologic inhibition of IKK2 results in a rapid induction of apoptosis with preferential depletion of B-cells and retention of myeloid cells and progenitors within the bone marrow.

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Emergence of Long-Lived Autoreactive Plasma Cells in the Spleen of Primary Warm Auto-Immune Hemolytic Anemia Patients Treated with Rituximab

Blood ◽

10.1182/blood.v124.21.569.569 ◽

2014 ◽

Vol 124 (21) ◽

pp. 569-569

Author(s):

Matthieu Mahevas ◽

Marc Michel ◽

Benoit Vingert ◽

Julien Moroch ◽

David Boutboul ◽

...

Keyword(s):

Bone Marrow ◽

B Cells ◽

B Cell ◽

Blood Cells ◽

Plasma Cells ◽

Cell Depletion ◽

B Cell Depletion ◽

Bone Marrow Plasma ◽

Previously Treated

Abstract Introduction: We recently proposed that B-cell depletion in immune thrombocytopenia (ITP) promotes the generation of long-lived plasma cells in the spleen, some of them being auto-reactive; but it remained possible that this observation was related to ITP itself rather than to B-cell depletion. Primary warm autoimmune hemolytic anemia (wAIHA) is a rare disease characterized by IgG auto-antibodies directed against antigens at the surface of red blood cells (RBCs) antigens, leading to their accelerated destruction. The use of B-cell depletion in wAIHA leads to 60 % to 70% of overall response at one-year and beyond. Nevertheless, 30-40 % of patients may resist to rituximab and then require a splenectomy. Nothing is known about antibody secreting cells (ASC) in the spleen of wAIHA patients, who have previously been treated or not with rituximab. In this study, we analyzed at the single cell level the splenic ASC from patients with chronic and active wAIHA, previously treated or not with rituximab (RTX), and we compared them with splenic ASC from ITP patients, and with splenic and bone marrow plasma cells from healthy donors (HD). Methods: We took advantage of the different therapeutic outcomes to analyze the splenic B-cell compartment of wAIHA patients, not previously treated with RTX (n=6), or after failure RTX treatment (n=3).Splenic tissues from organ donors and bone marrow from cardiovascular thoracotomy were used as controls. Blood samples from wAIHA (n=19), and (HD) (n=8) enrolled in this study were obtained after giving written informed consent in accordance with the Declaration of Helsinki. Results: We observed by flow cytometry and microscopy that the spleen from wAIHA patients who received less than 3 months of steroid therapy was the site of a B-cell response characterized by the presence of Bcl6+ germinal-center (GC) B-cells. Furthemore, splenic ASC secreted anti-red blood cell IgG in vitro. In line with this observation, we observed in the peripheral blood from patients with a newly diagnosed wAIHA (n=11), that short-lived IgG plasmablasts were increased compared with HD (n=8) (Mean 4.2 ± 0.84 % vs 0.99 ± 0.19% of CD19+ cells, p< 0.01). Moreover, for patients receiving long term steroid therapy (> 6 months) the plasmablast response was suppressed in the peripheral blood (Mean: 0.68 ± 0.2 % of CD19+ cells, n=8) and the splenic GC B-cell reaction was impaired (n=3). We conclude that short-lived IgG ASC result from an over-activity of GC reactions in wAIHA. We then analyzed the spleen of 3 patients who failed to respond to RTX, and observed a residual population of CD19+B-cells (median: 0.9% of lymphoid cells), including non-proliferative memory B-cells and plasma cells (PC). A fraction of these residual PC secreted anti-red blood cells IgG in vitro, thus accounting for the faillure of the B-cell depletion therapy. By using a single cell multiplex quantitative RT-PCR (Fluidigm dynamic arrays), we showed that such RTX-resistant plasma cells display a long-lived transcriptional program, which differs from PC from untreated wAIHA patients or HD, as well as from plasmablasts. Interestingly, the gene expression profile of wAIHA long-lived plasma cells segregated with long-lived PC previously observed in the spleen of ITP patients treated with rituximab. By a principal component analysis, we observed a gradient of maturation from plasmablasts to bone marrow plasma cells in which PC from RTX-treated spleens segregated close to bone marrow PC. We also observed that the cytokine BAFF was increased in the supernatants of spleen cell cultures from wAIHA patients treated with rituximab compared with controls (p< 0.05), suggesting, in keeping with our previous report in ITP, a role for BAFF in the differentiation of short-lived plasma cells into long-lived plasma cells. Conclusion: The presence of splenic long-lived autoreactive PC in wAIHA may explain why some patients cannot achieve a response after RTX. Our results show that, the B-cell depletion induced by rituximab itself, as opposed to the underlying auto-immune condition, promotes a suitable environment for the maturation of auto-immune long-lived plasma cells in the spleen. Targeting specifically some factors such as BAFF right after rituximab injection could be an interesting therapeutic option in the future. Disclosures No relevant conflicts of interest to declare.

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AML Relapse after Rituximab Treatment for Graft-Versus-Host Disease: Crucial Role for B Cells in Graft-Versus-Host and Graft-Versus-Leukemia

Blood ◽

10.1182/blood.v126.23.5473.5473 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5473-5473

Author(s):

Marijn Aletta Gillissen ◽

Sophie E. Levie ◽

Greta de Jong ◽

Etsuko Yasuda ◽

Arjen Q. Bakker ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

B Lymphocytes ◽

Cell Lines ◽

Cell Depletion ◽

B Cell Depletion ◽

Disease Relapse ◽

Graft Versus Host ◽

Graft Versus Leukemia ◽

Host Tissues

Abstract Patients with hematologic malignancies that develop graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HSCT) have a reduced risk of disease relapse compared to patients that do not develop GvHD, suggesting that GvHD and graft-versus-leukemia (GvL) responses are co-dependent. T cells are important in these processes, as T cell depletion from the graft reduces the risk of GvHD at the expense of disease relapse. Much less is known about the effect of B cell depletion on GvHD and GvL responses. Small patient series have demonstrated variable efficacy of Rituximab in the treatment of steroid-refractory chronic GvHD but the effect of depleting allo-reactive B cells on disease relapse remains to be determined. We here report on a patient with steroid-refractory GvHD whose AML relapsed after Rituximab treatment. This 39-year old male received an allogeneic HSCT for chemotherapy-related AML (AML-t) that however relapsed 8 weeks after the transplantation. Upon rapid cessation of immunosuppressive therapy (cyclosporine, mycophenolic acid) and without additional chemotherapy he obtained full remission, at the expense of severe GvHD of the skin, liver and intestine that was corticosteroid-refractory. B cell depletion with Rituximab was successful as second-line treatment for GvHD but eliminated the GvL response and the patient died of AML relapse several months after. To evaluate the B cell repertoire of this patient at the moment of maximal GvH and GvL responses, we isolated peripheral blood B lymphocytes that were transduced with Bcl-xL and Bcl-6 to create clonal B cell lines. These B cells were screened for binding to AML and host tissues. One clone was retrieved that specifically bound to AML cell lines and AML blasts freshly isolated from newly diagnosed AML patients. Antibodies from this clone induced antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity of AML cells in vitro. Several other clones were retrieved that were specific for host tissues such as liver (HepG2 and H69 cell lines), skin (primary fibroblasts) and/or colon (CaCo cell line). These data demonstrate the pivotal role of B lymphocytes in anti-leukemia and anti-host immune responses in an allogeneic HSCT recipient with relapsed AML-t. Disclosures No relevant conflicts of interest to declare.

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