B and NK Cells Closely Correlate with the Condition of Patients with Acute Pancreatitis

Purpose. Pancreatitis can lead to systemic inflammatory response, but the relationship between lymphocyte changes and patients with pancreatitis remains unclear. In this study, we evaluated the feedback function of changes in peripheral lymphocyte subsets on the condition of patients with pancreatitis. Materials and Methods. 131 acute pancreatitis (AP) patients and 11 chronic pancreatitis (CP) patients constituted the patients’ group; 20 healthy individuals were enrolled as healthy controls (HC). Serum concentration of C-reactive protein (CRP), amylase, and lipase and the frequency and absolute number of many types of peripheral lymphocytes (including T, B, NK, CD16+/CD56+ T, CD4+ T, CD8+ T, CD4+CD8+ T, and CD4−CD8− T cells) were detected on admission and the seventh day of standard treatment. Besides, the length of hospital stay was recorded. Results. The absolute number of all lymphocytes we studied decreased in patients with CP and in patients with almost all types of AP. The frequency change of lymphocytes varies among the different types of AP. During disease onset, B cell frequency correlated positively with CRP concentration and NK cell frequency correlated positively with amylase and lipase concentration. B cell frequency and CD4+ T cell absolute number were recovering towards normal after short-term treatment. The frequency of B cells and NK cells correlated positively with the length of hospital stay. Conclusions. B cells and NK cells closely correlate with patients’ condition and may help to diagnose AP more accurately and reflect treatment effect of AP in time, affecting the recovery speed of patients with M-AP, which may help physicians to better understand the pathophysiology of pancreatitis.

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Immunopathological characteristics of coronavirus disease 2019 cases in Guangzhou, China

10.1101/2020.03.12.20034736 ◽

2020 ◽

Cited By ~ 24

Author(s):

Yaling Shi ◽

Mingkai Tan ◽

Xing Chen ◽

Yanxia Liu ◽

Jide Huang ◽

...

Keyword(s):

T Cells ◽

B Cells ◽

Regulatory T Cells ◽

Hospital Stay ◽

Nk Cells ◽

Cd8 T Cells ◽

Immune Cell ◽

Length Of Hospital Stay ◽

Cell Types ◽

Respiratory Disorder

SummaryCoronavirus disease 2019 (COVID-19) is a respiratory disorder caused by the highly contagious SARS-CoV-2. The immunopathological characteristics of COVID-19 patients, either systemic or local, have not been thoroughly studied. In the present study, we analyzed both the changes in the cellularity of various immune cell types as well as cytokines important for immune reactions and inflammation. Our data indicate that patients with severe COVID-19 exhibited an overall decline of lymphocytes including CD4+ and CD8+ T cells, B cells, and NK cells. The number of immunosuppressive regulatory T cells was moderately increased in patients with mild COVID-19. IL-2, IL-6, and IL-10 were remarkably up-regulated in patients with severe COVID-19. The levels of IL-2 and IL-6 relative to the length of hospital stay underwent a similar “rise-decline”pattern, probably reflecting the therapeutic effect. In conclusion, our study shows that the comprehensive decrease of lymphocytes, and the elevation of IL-2 and IL-6 are reliable indicators of severe COVID-19.

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SARS-CoV-2 infection in acute pancreatitis increases disease severity and 30-day mortality: COVID PAN collaborative study

Gut ◽

10.1136/gutjnl-2020-323364 ◽

2021 ◽

pp. gutjnl-2020-323364

Author(s):

Sanjay Pandanaboyana ◽

John Moir ◽

John S Leeds ◽

Kofi Oppong ◽

Aditya Kanwar ◽

...

Keyword(s):

Acute Pancreatitis ◽

Hospital Stay ◽

Organ Failure ◽

Collaborative Study ◽

Length Of Hospital Stay ◽

Secondary Outcome ◽

Icu Admission ◽

Local Complications ◽

Persistent Organ Failure ◽

Increased Risk

ObjectiveThere is emerging evidence that the pancreas may be a target organ of SARS-CoV-2 infection. This aim of this study was to investigate the outcome of patients with acute pancreatitis (AP) and coexistent SARS-CoV-2 infection.DesignA prospective international multicentre cohort study including consecutive patients admitted with AP during the current pandemic was undertaken. Primary outcome measure was severity of AP. Secondary outcome measures were aetiology of AP, intensive care unit (ICU) admission, length of hospital stay, local complications, acute respiratory distress syndrome (ARDS), persistent organ failure and 30-day mortality. Multilevel logistic regression was used to compare the two groups.Results1777 patients with AP were included during the study period from 1 March to 23 July 2020. 149 patients (8.3%) had concomitant SARS-CoV-2 infection. Overall, SARS-CoV-2-positive patients were older male patients and more likely to develop severe AP and ARDS (p<0.001). Unadjusted analysis showed that SARS-CoV-2-positive patients with AP were more likely to require ICU admission (OR 5.21, p<0.001), local complications (OR 2.91, p<0.001), persistent organ failure (OR 7.32, p<0.001), prolonged hospital stay (OR 1.89, p<0.001) and a higher 30-day mortality (OR 6.56, p<0.001). Adjusted analysis showed length of stay (OR 1.32, p<0.001), persistent organ failure (OR 2.77, p<0.003) and 30-day mortality (OR 2.41, p<0.04) were significantly higher in SARS-CoV-2 co-infection.ConclusionPatients with AP and coexistent SARS-CoV-2 infection are at increased risk of severe AP, worse clinical outcomes, prolonged length of hospital stay and high 30-day mortality.

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P0032 VARIABLES AFFECTING LENGTH OF HOSPITAL STAY AND MORTALITY IN PATIENTS WITH ACUTE PANCREATITIS

European Journal of Internal Medicine ◽

10.1016/s0953-6205(09)60052-2 ◽

2009 ◽

Vol 20 ◽

pp. S19-S20

Author(s):

José Antonio Díaz-Peromingo ◽

Paula María Pesqueira-Fontán ◽

Marina Iglesias-Gallego ◽

Sonia Molinos-Castro ◽

Juan Saborido-Froján ◽

...

Keyword(s):

Acute Pancreatitis ◽

Hospital Stay ◽

Length Of Hospital Stay

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Tu1144 Comparison of Length of Hospital Stay of Children Admitted With Acute Pancreatitis Among Hospital Services At a Single Pediatric Tertiary Care Center

Gastroenterology ◽

10.1016/s0016-5085(14)62765-7 ◽

2014 ◽

Vol 146 (5) ◽

pp. S-765 ◽

Cited By ~ 1

Author(s):

Flora K. Szabo ◽

Joseph J. Palermo ◽

Tom K. Lin ◽

Maisam Abu-El-Haija

Keyword(s):

Acute Pancreatitis ◽

Hospital Stay ◽

Care Center ◽

Tertiary Care ◽

Length Of Hospital Stay ◽

Tertiary Care Center ◽

Hospital Services

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Phenotype of recovering lymphoid cell populations after marrow transplantation.

Journal of Experimental Medicine ◽

10.1084/jem.161.6.1483 ◽

1985 ◽

Vol 161 (6) ◽

pp. 1483-1502 ◽

Cited By ~ 139

Author(s):

K A Ault ◽

J H Antin ◽

D Ginsburg ◽

S H Orkin ◽

J M Rappeport ◽

...

Keyword(s):

T Cell ◽

B Cells ◽

B Cell ◽

Nk Cells ◽

Cell Types ◽

Lymphoid Cells ◽

The Other ◽

Hla Dr ◽

T Cell Antigens ◽

Leu 7

Four patients who received bone marrow transplants were studied sequentially during the posttransplant period to define the pattern of recovering lymphoid cell types. Three patients received T cell-depleted, HLA-matched marrow, and one received untreated marrow from an identical twin. Blood lymphoid cells were labeled with 25 different pairs of monoclonal antibodies. In each sample, one antibody was conjugated to fluorescein and one to phycoerythrin, thus allowing simultaneous assessment of the expression of the two markers using the fluorescence activated cell sorter. A total of 14 antibodies were used, routinely including HLE, Leu-M3, Leu-4, Leu-1, Leu-5, Leu-9, Leu-6, Leu-2, Leu-3, HLA-DR, Leu-7, Leu-11, Leu-15, and Leu-12. Other antibodies were used to further define some populations. This study has allowed us to define six distinct cell types that have appeared in all four patients by day 90 posttransplantation, and which account for 90-100% of all circulating lymphoid cells. These cell types are (a) T helper cells expressing Leu-1, Leu-4, Leu-9, Leu-5, Leu-3, and variable amounts of HLA-DR; (b) T suppressor cells expressing Leu-1, Leu-4, Leu-9, Leu-5, Leu-2, and variable amounts of HLA-DR; (c) B cells expressing Leu-12, B1, HLA-DR, IgD, and IgM, but none of the T cell antigens; (d) an unusual B cell phenotype (Leu-1 B) expressing all of the B cell markers, and also having low amounts of Leu-1, but none of the other T cell antigens; (e) natural killer (NK) cells expressing Leu-11, Leu-15, Leu-5 but none of the other T cell or B cell markers; (f) NK cells expressing Leu-11, Leu-15, Leu-5, and low levels of Leu-2. Both NK types also express Leu-7 on some, but not all cells. The relative frequencies of these cell types varied among the patients and with time, but the striking findings were the presence of relatively few mature T cells, large numbers of NK cells, and the preponderance of the unusual Leu-1 B cell over conventional B cells in all three patients who developed B cells. Sorting experiments confirmed the NK activity of the major NK cell phenotypes, and DNA analysis confirmed that all of the cells studied were of donor origin. In addition, analysis of Ig genes in one patient showed that the Leu-1 B cells were not clonally rearranged.(ABSTRACT TRUNCATED AT 400 WORDS)

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Suppressing Synthesis of the Long Isoform of the Prolactin Receptor Is a Targeted Strategy to Prevent and Treat B Cell Malignancies

Blood ◽

10.1182/blood-2021-147055 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1135-1135

Author(s):

Adeleh Taghi Khani ◽

Anil Kumar ◽

Kelly Radecki ◽

Sung June Lee ◽

Mary Lorenson ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Nk Cells ◽

Malignant Transformation ◽

Nk Cell ◽

B Cell Lymphoma ◽

B Cell Malignancies ◽

Autoreactive B Cells ◽

Cell Numbers ◽

Bcl2 Expression

Abstract Rationale B cell malignancies, including leukemia and lymphoma, are high-risk lymphoid neoplasms. B cell malignancies predispose to autoimmune diseases including systemic lupus erythematosus (SLE) which increase the risk of developing these malignancies by >5-fold. Increased prolactin (PRL) expression is known to exacerbate SLE and promote the survival of autoreactive B cells. Furthermore, PRL induces expression of the protooncogenes, MYC and BCL2, in lymphoid tissues. However, whether PRL drives the initiation and maintenance of B cell malignancies was not known. Results We first tested our hypothesis that PRL, specifically signaling through the pro-proliferative and anti-apoptotic long isoform (LF) of the PRL receptor (PRLR), drives the progression of SLE to B cell malignancies. To this end, we knocked down the LF PRLR in MRL-lpr mice predisposed to developing SLE using a splice-modulating oligomer (SMO) that blocks splicing to produce the LF PRLR without affecting the short isoforms. LF PRLR knockdown reduced splenic and circulating B cell numbers in MRL-lpr SLE mice (Fig.1a). Consistent with reduced B cell numbers, BCL2 expression in B cells of SLE mice was suppressed after LF PRLR knockdown, although MYC was unaltered (Fig.1b). By sequencing the immunoglobulin heavy chains (IGH), we compared the composition of the splenic B cell repertoire between control- and LF PRLR SMO-treated SLE mice. Control oligomer treated SLE mice accumulated splenic B cells with long complementary determining region 3 (CDR3) and B cells with non-functional IGH, characteristics of autoreactive B cells. Treatment with the LF PRLR SMO reduced both. We then measured the expression of enzymes known to induce malignant transformation of B cells, namely recombination activating genes 1/2 (RAG1/2) and activation-induced cytidine deaminase (AID), in B cells of SLE mice in controls versus LF PRLR knockdown. Importantly, LF PRLR knockdown significantly reduced RAG1 (Fig.1c) and AID expression in splenic B cells of SLE mice (Fig.1d,e). Our findings thus underscore a causal role for LF PRLR signaling in promoting of malignant transformation of B cells in SLE. Because PRL induces the expression of BCL2 and MYC in lymphocytes, we next determined whether LF PRLR promotes the survival of overt B cell malignancies that overexpress MYC and BCL2, including diffuse large B cell lymphoma (DLBCL) and B-cell acute lymphoblastic leukemia (B-ALL). We observed that B-lymphoblasts expressed significantly higher levels of PRL and the LF PRLR as compared to normal B cells (Fig.1f). We also found that higher expression of PRL at diagnosis predicts poor clinical outcome in DLBCL patients (P=0.0244), and that patients with MYC/BCL2-overexpressing ALLs with a poor prognosis had significantly higher expression of the LF PRLR compared to their MYC lowBCL2 low counterparts (P<0.0001). These observations suggested that LF PRLR may modulate MYC and BCL2 expression. Knockdown of the LF PRLR using the LF PRLR SMO in MYC/BCL2-driven human B cell malignancies killed lymphoblasts and reduced MYC and BCL2 protein levels (Fig.1g). Because we previously showed that MYC-driven lymphoid malignancies are sensitive to natural killer (NK) cell-mediated immune clearance, we also examined whether LF PRLR knockdown synergized with NK cells in killing DLBCL. We found that LF PRLR knockdown enhanced NK cell-mediated killing of B-lymphoblasts (Fig.1h). Of note, no reductions were observed in NK cell viability or MYC levels within NK cells upon LF PRLR knockdown, suggesting that LF PRLR selectively kills B-lymphoblasts without negatively impacting NK homeostasis. Conclusion Our studies identify the specific knockdown of LF PRLR as a potentially safe and targeted strategy to prevent the onset of B cell malignancies in SLE patients and to treat flagrant DLBCL and B-ALL. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Role of early enteral feeding in mild and moderate acute pancreatitis

International Surgery Journal ◽

10.18203/2349-2902.isj20214376 ◽

2021 ◽

Vol 8 (11) ◽

pp. 3387

Author(s):

Aswin George Roy ◽

Haridas T. V.

Keyword(s):

Acute Pancreatitis ◽

Hospital Stay ◽

Enteral Feeding ◽

Significant Risk ◽

Length Of Hospital Stay ◽

Advantages And Disadvantages ◽

Early Enteral Feeding ◽

Systemic Complication ◽

Infective Complications

Background: Timing of enteral feeding in acute pancreatitis was always a matter of controversy. Increasing evidence suggests that early enteral feeding reduces systemic and local complications of pancreatitis and thereby hospital stay. Hence the study has been undertaken to determine the feasibility, advantages and disadvantages of early enteral feeding in mild and moderate acute pancreatitis. Methods: Patients admitted with symptoms and signs suggestive of mild and moderate acute pancreatitis who were started on early enteral feeding (within 48 hours of admission) were included in study. Blood investigation results are used to classify patients accordingly to mild and moderate acute pancreatitis based on Ransons’s score. Patients were followed up and categorized based on development of complications, length of hospital stay.Results: Majority of the patients who were started on early enteral feeding showed significant decrease in complications and hospital stay. Study also suggested that age is a significant risk in development of complications. Gender is not significant in the development of complications.Conclusions: There is significant decrease in rate of systemic complication, local infective and non-infective complications, length of hospital stay among acute pancreatitis patients who were started on early enteral feeding (within 48 hours).

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Multidimensional Flow Cytometric (MFC) Analysis of the Immune System of Multiple Myeloma (MM) Patients Achieving Long Term Disease Control

Blood ◽

10.1182/blood.v118.21.810.810 ◽

2011 ◽

Vol 118 (21) ◽

pp. 810-810

Author(s):

Roberto J. Pessoa Magalhaes ◽

María-Belén Vidriales ◽

Bruno Paiva ◽

Maria-Victoria Mateos ◽

Norma C. Gutierrez ◽

...

Keyword(s):

T Cells ◽

Immune System ◽

B Cells ◽

Disease Control ◽

B Cell ◽

Nk Cells ◽

Cell Populations ◽

High Dose ◽

Newly Diagnosed

Abstract Abstract 810FN2 Increasing evidence shows that a small fraction of MM patients (pts) treated with high-dose therapy followed by autologous stem cell transplantation achieve long-term remission. Interestingly, this is not restricted to pts in complete response (CR), since those that revert to a monoclonal gammopathy of undetermined significance (MGUS) profile may also achieve long-term remission, despite the persistence of residual myeloma plasma cells (PCs). These results suggest that in addition to the anti-myeloma therapy, other factors may play a role in the control of the disease. Herein, we used 8-color MFC for detailed characterization of the structural components of the immune system and hematopoietic precursor cells (HPC) in paired bone marrow (BM) and peripheral blood (PB) samples from 26 MM patients in long-term disease control (LTDC): 9 in continuous CR and 17 who reverted to an MGUS profile and that subsequently showed stable disease without treatment for ≥5 years (median of 9 years; range, 5–19). As controls, paired BM and PB samples from 23 newly-diagnosed MGUS and 16 MM pts, together with 10 healthy adults (HA), were studied in parallel. In all BM and PB samples the distribution of the major T- (CD4, CD8, Tregs and γδ), NK- (CD56dim and CD56bright) and B-cell subsets (Pro-B, Pre-B, naïve and memory), in addition to normal PCs, dendritic cell (DC) subsets (plasmacytoid, myeloid and monocytic), monocytes, and CD34+ HPC (myeloid and lymphoid), were studied. The percentage and absolute count of each cell population was analysed in the BM and PB, respectively. Comparison of the two groups of MM pts with LTDC (9 CR vs. 17 MGUS-like) showed similar (p>.05) cellular profiles in PB and BM, except for an increased number of BM and PB normal PCs in CR patients (P≤.04). Consequently, for all subsequent analyses, LTDC myeloma pts were pooled together. When compared to HA, patients with LTDC had increased numbers of CD8 T-cells and CD56dim NK-cells in both the BM and PB (p≤.03 and p≤.01, respectively). Despite this, the distribution of BM and PB CD4, CD8 and γδ T-cells among LTDC patients was similar (p>.05) to that of both newly-diagnosed MM and MGUS cases; in contrast, BM and PB Tregs were significantly decreased vs newly-diagnosed MM (P=.03) and MGUS (P=.04). Regarding B-cells and normal PCs, LTDC patients showed increased numbers of BM B-cell precursors (both Pro-B and Pre-B cells) and normal PCs vs. newly diagnosed MM (P≤.05), but not MGUS, together with increased numbers of naïve B-cells vs. both MM and MGUS pts (P≤.01); all such cell populations returned to levels similar (p>.05) to those of HA. As expected, this also included the number of CD34+ B-cell HPC which was increased among patients who achieved LTDC vs MM (p=.02), at levels similar (p>.05) to those of MGUS and HA. Regarding DC, LTDC patients showed normal DC numbers in PB (but with higher PB myeloid-DC numbers vs. MM; p=.02), in association with decreased numbers of plasmacytoid DC and increased monocytic-DC in the BM vs. HA (p≤.04). No differences were found for the numbers of BM and PB monocytes. In summary, here we investigated for the first time the immune cell profile of MM patients who achieve long-term disease control. Our results show that, as newly-diagnosed MM, patients that achieve long-term disease control also show increased numbers of cytotoxic T-cells and CD56dim NK-cells; however, in contrast to newly-diagnosed MM, among LTDC patients such increase is associated with lower numbers of T-regs and an almost complete recovery of the normal PC, B-cell precursor and naïve B-cell compartments both in BM and PB. Further investigations on the activation and functional status of these cell populations are warranted.MO (%)/SP (cels./μl)HA N= 10MGUS N= 23MM N= 16LTDC-MM N= 26T cells9.588110.6117313113711926 CD4+4.85004.6624^6*5085463 CD8+3.7∼216∼4.63865.32645.3431 TCR γδ.2426.3230.2428.3421 Treg.4137.4141^.54*38.3432NK cells.7∼87∼1.51982.11721.6212 CD56 dim.65∼79∼1.41922.21681.6202B cells2.81471.8104.97*68*1.9160 Pro B.11—.06—.02*—.07— Pre B.6—.4—.08—.23— Naive SP—80—57^—36*—118 Normal-PCS.18.9.11.7.008.72*.11.84DCs.3449.3653.6848.558 Monocytes2.22472.42853.43023.1315 m-DC SP—11—14—8*—12 MO-DC.11∼29.2036.434.2837 p-DC.2∼4.1.145.112.8.123.8CD34+.9∼1.46.61.1.261.4.431.4 Mie-HPC.8∼—.53—.26—.36— Linfo-HPC.1—.07—.03*—.05—*p≤.05 LTDC vs MM: ^ p≤.05 LTDC vs MGUS; ∼ p≤.05 LTDC vs HA Disclosures: Paiva: Jansen-Cillag: Honoraria; Celgene: Honoraria. Martinez:Janssen: Honoraria; Celgene: Honoraria. Maiolino:Centocor Ortho Biotech Research & Development: Research Funding.

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Pathological Roles of p18 Deficiency Toward B Cell Malignances

Blood ◽

10.1182/blood.v126.23.2448.2448 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2448-2448

Author(s):

Sha Hao ◽

Fang Dong ◽

Wen Zhou ◽

Hui Cheng ◽

Shihui Ma ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Poor Prognosis ◽

Absolute Number ◽

Cell Development ◽

B Cell Development ◽

B Cell Malignancies ◽

Hematopoietic Stem ◽

Hematopoietic Malignancies ◽

Low Expression

Abstract The cyclin-dependent kinases inhibitor CDKN2C (p18INK4C, p18) is a member of the INK4 family that specifically blocks the activity of CDK4/6 in the G1 phase of cell cycle. In the hematopoietic system, deletion of p18 was indicated to be associated with T cell malignancies in mice and B cell malignancies in humans. Moreover, p18 deficiency is a poor prognosis factor for the patients with multiple myeloma (MM). However, a formal investigation on the pathological roles of p18 deficiency in hematopoietic malignancies, especially B cell malignancies is lacking. In this study, we first obtained direct clinical relevance of p18 deficiency with hematopoietic malignancies. Based on the Oncomine data set analysis, low expression of p18 was found in the patients with B-Cell Acute Lymphoblastic Leukemia (54 out of 80). In addition, by Gene expression Profile (GEP) analysis (n=361) and multi-color FISH analysis (n=265) of first-visit MM patients, there were 11% MM patients showed low expression and 9.06% biallelic deletion of p18 gene respectively, which was correlated with poor prognosis. Further analysis indicated higher expression of c-Myc, Bcl-2 and TRAF3 in p18-deleted MM patients or MM cell lines. We then focused on the impact of p18 deletion on B cell development with the mice deficient in p18 (p18-/-). The frequency and absolute number of B220+ B cell were significantly decreased in the bone marrow (21.075±0.168% vs 13.956±1.613%, n=5) or spleen (49.320±1.773 vs 35.35±1.673, n=5) of p18-/- mice. Secretion of immunoglobulin (Ig) from plasma cells was also impaired. Furthermore, p18-/- BM or enriched hematopoietic stem cell (LSK+) transplantation also recaptured the deficiency of mature B cells in the recipients despite higher repopulation in the p18-/- group. Ectopic over-expression of p18 in the hematopoietic stem and progenitor cells (HSPCs) via retroviral transduction could partially correct the abnormality of p18-/- B cells in the transplant recipients. These results suggested that the defect of B cell development in the absence of p18 was intrinsic to the hematopoietic cells, rather than extrinsic (via micro-environmental). To further define the effects of p18 deficiency on HSPCs prior to B cell commitment, we enumerated the frequencies of LT-HSC, MPP, CMP, GMP, MEP, Lin-IL-7R+ and CLP cell populations in p18-/- or control mice. There was no significant difference in the frequency or absolute number of CMP, GMP, MEP, or CLP between p18-/- and control groups. Notably however, the colony-forming cells of pre-B cells in p18-/- BM were significantly increased (24.4±2.1 vs 32.6±1.8, n=5). Moreover, we also examined the B cells at different developmental stages including pre-pro-B cell, pre-B, immature-B and mature B cells in BM, as well as transitional stage 1(T1), transitional stage 2 (T2) and mature B cells in the spleen. Our data showed an accumulation of the cells at pre-B cell stage in the absence of p18, while dramatically decreased at mature B cells stage. To further explore the molecular basis, single cell RT qPCR analysis was performed and revealed that the transcription factors including Foxo1, Rag2, E2A, EBF1and Pax5 were significantly higher inCLP, pro-B, pre-B, immature-B subpopulations of p18-/- group. However, lamada 5, which is necessary for B cells maturation, was remarkably decreased in p18-/- immature B cells compared with control group. Taken together, our study provides definitive evidence for the disruption of B cell development due to p18 deficiency and this new evidence underlies the pathological contributions of p18 down-regulation or deletion to B cell malignancies in humans. Disclosures No relevant conflicts of interest to declare.

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