Calreticulin (CRT) is a multifunctional molecule in both intracellular and extracellular environment. We have previously found that a recombinant CRT fragment (rCRT/39-272) could modulate T cell-mediated immunity in mice via activation and expansion of CD1d(hi)CD5⁺ B cells as well as induction of CRT-specific regulatory antibodies. Antibody secreting cells (ASCs) are terminally differentiated B cells responsible for producing antibodies to participate in positive immune response as well as immune regulation. In this study, we demonstrate that rCRT/39-272 differentiates murine CD1d(hi)CD5⁺ B cells into ASCs marked by increased expression of plasma cell-associated transcription factors and production of polyreactive antibodies against DNA and CRT in vitro. Intraperitoneal administration of rCRT/39-272 augmented differentiation of CD1d(hi)CD5⁺ B cells into ASCs in naïve mice or mice with experimental autoimmune encephalomyelitis. Thus, we propose that ASC differentiation and subsequent antibody production of CD1d(hi)CD5⁺ B cells are key steps in CRT-mediated immunoregulation on inflammatory T cell responses.
Animals ; Antigens, CD1d ; metabolism ; Autoantibodies ; biosynthesis ; B-Lymphocytes ; cytology ; drug effects ; immunology ; metabolism ; CD5 Antigens ; metabolism ; Calreticulin ; chemistry ; Cell Differentiation ; drug effects ; Encephalomyelitis, Autoimmune, Experimental ; immunology ; Humans ; Mice ; Peptide Fragments ; chemistry ; pharmacology ; Solubility

The coexistence of CCND1/IGH and MYC rearrangements in mantle cell lymphoma (MCL) is a rare finding associated with a very poor prognosis. In this study, a patient with blastoid variant (MCL) is reported. The disease was clinically aggressive and refractory to chemotherapy, and the patient only survived for 1 month following diagnosis. Conventional cytogenetic study, FISH, and multicolor FISH (mFISH) demonstrated the involvement of the BCL1/CCND1 locus in a complex translocation, t(3;11)(q25;p15)t(11;14)(q13;q32). In addition, subclonal abnormalities in the 8q24 region, manifested as a t(8;14)(q24;q32)/MYC rearrangement, were identified. To the best of our knowledge, this is the first MCL case in Korea bearing these complex genomic aberrations.
Aged, 80 and over ; Antigens, CD5/*metabolism ; Bone Marrow/immunology/metabolism ; Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 14 ; Chromosomes, Human, Pair 3 ; Gene Rearrangement ; Humans ; Immunophenotyping ; In Situ Hybridization, Fluorescence ; Lymphoma, Mantle-Cell/*diagnosis/genetics/immunology ; Male ; Oncogene Proteins, Fusion/*genetics ; Proto-Oncogene Proteins c-myc/*genetics ; Translocation, Genetic

OBJECTIVETo investigate the number of peripheral blood CD5(+) B cells and their ability of secreting IL-10 in patients with immune thrombocytopenia (ITP).

METHODSPeripheral blood lymphocytes were isolated from 57 pre-treated, 40 post-treated ITP patients and 25 controls using Ficoll-Hypaque density centrifugation and then stained with PE-CD5/FITC-CD19 for flow cytometric analysis. After 24-hour culture, lymphocytes were stained with APC-IL-10 for intracellular cytokine detection. ELISA assay was employed to determine IL-10 concentration in supernatants.

RESULTSThe percentage and absolute number of CD5(+) B cells in peripheral blood from pre-treated ITP patients were significantly higher than that from normal controls (3.75 ± 2.37)% vs (2.10 ± 1.08)%, P < 0.01; (6.29 ± 5.77)× 10(7)/L vs (3.06 ± 1.90)× 10(7)/L, P < 0.01. CD5(+) B cells expressed more intracellular IL-10 than other lymphocyte subsets both in ITP patients and normal controls. The percentages of IL-10(+) cells within CD5(+) B cells in pre-treated ITP patients and normal controls were (29.51 ± 20.73)% and(15.90 ± 9.58)%, respectively(P < 0.01). Intracellular mean fluorescence intensity (MFI) of IL-10 in CD5(+) B cells was 27.95 ± 13.99 in pre-treated patients, which was significantly higher than that in controls (P < 0.01). In contrast, IL-10 concentration in supernatants was (173.05 ± 102.50) ng/L in pre-treated ITP group, which was lower than that (230.61 ± 76.96) ng/L in controls. In patients who achieved remission, the number of CD5(+) B cells decreased to level comparable to normal controls. While intracellular IL-10 MFI of CD5(+) B cells in post-treated ITP patients remained as high as in pre-treated ones, the IL-10 concentration in supernatants increased to level similar to controls.

CONCLUSIONThe significantly increased number of CD5(+) B cells and accumulated IL-10 in CD5(+) B cells suggested impaired IL-10 secretion in ITP patients. The number and the ability of secreting IL-10 of CD5(+) B cells could be restored after effective treatments in patients with ITP.

Adult ; Aged ; B-Lymphocytes ; immunology ; metabolism ; CD5 Antigens ; metabolism ; Case-Control Studies ; Female ; Humans ; Interleukin-10 ; blood ; Male ; Middle Aged ; Purpura, Thrombocytopenic, Idiopathic ; blood ; immunology ; Young Adult

IL-10 production by CD19(+)CD5(+) B cells was investigated, by determining the expression levels of CD19, a classical B cell marker. Peripheral mononuclear cells were stained with fluorescence-conjugated anti-CD5, anti-CD19, anti-IL-10, and Annexin V. Interestingly, IL-10-producing B cells were found to be localised within the CD19(low)CD5(+) B cell subset. Apoptotic changes were also observed mainly in CD19(low) cells among B cells. Thus, CD5(+) B cells should be classified as CD19(high) and CD19(low) cells, and the immunological significance of CD19 for the IL-10 production by CD5(+) B cells requires further studies.
Antigens, CD19/metabolism ; Antigens, CD5/metabolism ; Apoptosis/immunology ; B-Lymphocyte Subsets/cytology/*immunology ; Cell Separation ; Flow Cytometry ; Humans ; Interleukin-10/*biosynthesis

Waldenstrom macroglobulinemia (WM) is a B-cell lymphoproliferative disorder associated with bone marrow involvement of lymphoplasmacytic lymphoma (LPL) and an IgM monoclonal gammopathy. Generally B-lymphocytes in LPL do not express CD5 that is important for differential diagnosis of B-cell lymphoproliferative disorders. In WM, various renal diseases and type I cryoglobulinemia are well described separately, but cryoglobulinemic glomerulonephropathy is very rarely reported. A 61-yr-old woman complained of generalized edema, cyanosis of the extremities in cold weather, visual disturbance, and pancytopenia. Bone marrow and renal biopsy showed CD5+ expressing B-cells and cryoglobulinemic glomerulonephropathy. With the diagnosis of WM, she received cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy and got complete remission. Here, we report a rare case of WM associated with unusual expression of CD5+ B-lymphocytes and cryoglobulinemic glomerulonephropathy, and emphasize the importance of the clinical features in differentiating CD5+ B-cell lymphoproliferative disorders.
Antigens, CD5/*metabolism ; Antineoplastic Agents/therapeutic use ; B-Lymphocytes/immunology/metabolism ; Bone Marrow/pathology ; Cryoglobulinemia/diagnosis ; Cyclophosphamide/therapeutic use ; Diagnosis, Differential ; Doxorubicin/therapeutic use ; Drug Therapy, Combination ; Female ; Glomerulonephritis/*diagnosis/pathology ; Humans ; Kidney/pathology ; Middle Aged ; Paraproteinemias/diagnosis ; Prednisolone/therapeutic use ; Vincristine/therapeutic use ; Waldenstrom Macroglobulinemia/*diagnosis/drug therapy/pathology

OBJECTIVETo study the possible loss of pan-T cell antigens CD2, CD3, CD5 and CD7 in Kikuchi's disease and to evaluate the role of T cell antigen loss in distinguishing benign from malignant T-cell lymphoid lesions.

METHODSFormalin-fixed and paraffin-embedded tissues of 33 cases of Kikuchi's disease and 15 cases of reactive lymphoid hyperplasia were studied by EliVision immunohistochemical staining for CD2, CD3, CD5 and CD7.

RESULTSTwenty-four of the 33 (72.7%) cases of Kikuchi's disease lost one or more of the pan-T cell antigens, including the loss of CD5 only (13 cases), CD7 only (1 case), CD2 only (1 case), CD2 and CD7 (2 cases), CD5 and CD7 (4 cases), CD2 and CD5 (2 cases), and CD2, CD7 and CD5 (1 case). Amongst these cases, the commonest antigen loss was CD5 (20 cases, 60.6%), followed by CD7 (8 cases, 24.2%) and CD2 (6 cases, 18.2%). Compared with the xanthomatous subtype of Kikuchi's disease, the loss of antigens was more commonly seen in the proliferative and necrotizing subtypes. Analysis of follow-up data showed that the loss of antigens in Kikuchi's disease was not significantly associated with the prognosis. In reactive lymphoid hyperplasia, the expression of CD2, CD3, CD5 and CD7 was seen in all cases with similar intensity, with no obvious pan-T cell antigen loss.

CONCLUSIONLoss of one or more pan-T cell antigens in Kikuchi's disease is demonstrated in present study, suggesting that the immunophenotypic pattern is not unique in T cell lymphoma.

Adolescent ; Adult ; Antigens, CD7 ; metabolism ; CD2 Antigens ; metabolism ; CD3 Complex ; metabolism ; CD5 Antigens ; metabolism ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Histiocytic Necrotizing Lymphadenitis ; immunology ; pathology ; Humans ; Male ; Middle Aged ; Pseudolymphoma ; immunology ; Recurrence ; T-Lymphocytes ; immunology ; Young Adult

BACKGROUNDThe cause of late-onset hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains obscure. In clinical practice, some LOHC patients respond to immunosuppression. The aim of this study was to determine the immune pathogenesis of LOHC post allo-HSCT.

METHODSWith the diagnosis of LOHC, patients were given initial treatment consisting of fluid hydration, alkalization and forced diuresis, and empirical anti-viral therapy for 10 - 14 days or until a week after the virus became negative. The nonresponders were applied corticosteroid. Seven to ten days later, patients' response was evaluated. Along with treatment, CD19(+) B lymphocyte subsets were measured at various study points.

RESULTSFrom October 2009 to March 2010, we found 28 cases of LOHC occurred in 25 patients who underwent allo-HSCT in our hospital. Except that three cases were not treated according to the protocol, the other 25 cases were divided into three groups: anti-virus responders (Group A, n = 6), corticosteroid responders (Group B1, n = 16), corticosteroid and anti-virus nonresponders (Group C, n = 3) according to their clinical response. Percentages of CD19(+)CD5(+) B lymphocytes were not significantly different among three groups at onset of LOCH. However, in Group B1 after the first anti-virus phase, percentages of CD19(+)CD5(+) lymphocytes significantly increased comparing with those at onset (P = 0.022), and then significantly decreased at PR (P = 0.003) and CR (P = 0.002) with corticosteroid treatment. But significant change was not observed in Groups A and C.

CONCLUSIONThe immune etiology seems to be involved in the development of LOHC and the proportion of CD19(+)CD5(+) lymphocytes may serve as a cellular biomarker to predict the response to corticosteroid in LOHC.

Adolescent ; Adrenal Cortex Hormones ; therapeutic use ; Adult ; Antigens, CD19 ; metabolism ; B-Lymphocytes ; metabolism ; CD5 Antigens ; metabolism ; Child ; Child, Preschool ; Cystitis ; drug therapy ; immunology ; therapy ; Female ; Flow Cytometry ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Young Adult

OBJECTIVETo study the clinicopathologic characteristics of thymic epithelial tumors and to evaluate the diagnostic reproducibility and clinical relevance of the 2004 WHO histologic classification system.

METHODSThe morphology and immunophenotype of 52 cases of thymic epithelial tumor were reviewed. The tumors were classified according to the new WHO classification system and the clinical data were analyzed.

RESULTSOf the 52 cases studied, 45 were thymomas and 7 were thymic carcinomas. Amongst the 45 cases of thymoma, 6 (13.4%) were type A, 15 (33.3%) were type AB, 4 (8.9%) were type B1, 9 (20.0%) were type B2, 9 (20.0%) were type B3 and 2 (4.4%) were metaplastic thymoma. Amongst the 7 cases of thymic carcinoma, 6 were squamous cell carcinomas and 1 was neuroendocrine carcinoma. The commonest presentations were cough and chest pain. Some cases were incidentally discovered by routine physical examination. Thirteen cases (25.0%) of thymoma were associated with myasthenia gravis. CT scan showed that 49 cases (94.2%) were located in the anterior mediastinum. All cases of type A, AB and B1 thymoma and most cases of B2 thymoma appeared as well-defined homogeneous mass, whereas a few cases of type B2 thymoma and most cases of type B3 thymoma and thymic carcinoma were poorly demarcated and heterogeneous. According to Masaoka staging system, 20 cases (41.7%) belonged to stage I, 15 cases (31.3%) stage II, 11 cases (22.9%) stage III and 2 cases (4.1%) stage IV. The histologic subtypes of thymic epithelial tumors significantly correlated with the clinical stages (chi(2) = 32.5, P < 0.01).

CONCLUSIONSThe 2004 revision of WHO histologic classification system for thymic epithelial tumors shows a high degree of reproducibility. Correlation with the radiologic, clinical and prognostic parameters is helpful in determining the management strategy for individual patients.

Adult ; Aged ; Antibodies, Monoclonal ; analysis ; Antigens, CD20 ; metabolism ; CD5 Antigens ; metabolism ; Carcinoma, Neuroendocrine ; classification ; diagnostic imaging ; metabolism ; pathology ; Carcinoma, Squamous Cell ; classification ; diagnostic imaging ; metabolism ; pathology ; Female ; Follow-Up Studies ; Humans ; Keratins ; immunology ; Male ; Middle Aged ; Myasthenia Gravis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis ; Radiotherapy, Adjuvant ; Retrospective Studies ; Thymoma ; classification ; diagnostic imaging ; metabolism ; pathology ; Thymus Neoplasms ; classification ; diagnostic imaging ; metabolism ; pathology ; Tomography, X-Ray Computed

OBJECTIVETo study the clinicopathologic features, immunophenotype and prognosis of primary cutaneous anaplastic large cell lymphoma (C-ALCL).

METHODSEight cases of C-ALCL were enrolled into the study. The clinicopathologic features, immunohistochemical findings and results of in-situ hybridization for EBER 1/2 were analyzed.

RESULTSThree of the 8 patients were males and 5 were females. The median age was 49.5 years. C-ALCL often presented with solitary skin nodule, without systemic symptoms. Histologically, the lymphoma cells infiltrated the dermis and subcutis in a sheet-like pattern. They were of large size and showed conspicuous nuclear atypia. Immunohistochemical study showed that more than 75% of the lymphoma cells were positive for CD30. All cases expressed one to three T cell markers (CD3, CD5 or CD45RO) and cytotoxic granule-associated antigens (TIA-1, granzyme B or perforin). The staining for leukocyte common antigen was positive in all cases, while the expression of CD5, CD8, ALK-1 and epithelial membrane antigen was noted in 5, 1, 1 and 3 cases, respectively. The staining for CD15, CD20, CK and HMB45 was negative. In-situ hybridization for EBER 1/2 was also negative in all the cases studied. Follow-up information was available in 6 patients. Five of them were still alive and 1 died of unclear cause.

CONCLUSIONSC-ALCL has distinctive clinicopathologic and immunophenotypic features. It is not Epstein-Barr virus-related and often carries a favorable prognosis.

Adult ; Aged ; CD5 Antigens ; metabolism ; Child ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Immunophenotyping ; In Situ Hybridization ; Ki-1 Antigen ; metabolism ; Leukocyte Common Antigens ; metabolism ; Lymphoma, Primary Cutaneous Anaplastic Large Cell ; immunology ; metabolism ; pathology ; therapy ; Male ; Middle Aged ; Prognosis ; RNA, Viral ; metabolism ; Skin Neoplasms ; immunology ; metabolism ; pathology ; therapy ; Young Adult

The aim of study was to investigate the lymphocyte changes in peripheral blood of patients with Graves's disease accompanied by hematocytopenia and to explore its pathogenesis. The quantity and ratio of Th(2), Th(1), CD5(+) B, Bcl-2 level in 24 Graves's disease patients with hematocytopenia were detected by FACS, and 18 adults were selected as normal controls. The results indicated that the percentages of Th(1), Th(2), ratio of Th(2)/Th(1), CD5(+) B, Bcl-2 level in peripheral blood of the patients were (0.81 +/- 0.45)%, (6.83 +/- 3.02)%, (20.55 +/- 6.15)%, (20.89 +/- 1.62)%, (80.25 +/- 15.56)%, respectively, and were higher than those of normal controls [(0.39 +/- 0.24)% (P<0.05), (0.28 +/- 0.15)% (P<0.01), (0.52 +/- 0.12)% (P<0.01), (7.89 +/- 0.38)% (P<0.05), (36.49 +/- 6.79)% (P<0.05)]. It is concluded that the pathogenesis of Graves's disease with hematocytopenia may be related to unbalance of Th(1)/Th(2), increase of Th(2) inducing over-expression of CD5(+) B and Bcl-2 on B cell.
Adolescent ; Adult ; B-Lymphocytes ; immunology ; metabolism ; CD5 Antigens ; immunology ; Female ; Graves Disease ; complications ; immunology ; Humans ; Male ; Middle Aged ; Pancytopenia ; complications ; immunology ; Proto-Oncogene Proteins c-bcl-2 ; biosynthesis ; Th1 Cells ; immunology ; Th2 Cells ; immunology