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Immunotoxin-Mediated Depletion of CD5+ T Cells from Bone Marrow for Graft-vs.-Host Disease Prophylaxis
Published in Adrian P. Gee, BONE MARROW PROCESSING and PURGING, 2020
Joseph H. Antin, Howard J. Weinstein, Cyril Bouloux, Barbara E. Bierer
We and others have purged the marrow of T cells using monoclonal antibodies (mAb) to the cell surface protein CD5.19–22 CD5 is a human T cell antigen that is found on the majority of mature T cells. It is not found on natural killer (NK) cells, some T cells expressing the γ/δ T cell receptor (TCR), nor a small population of T cells expressing the α/β TCR. By purging the marrow with an anti-CD5 mAb, we spared NK cells and CD-5+ T cells. Normal individuals have from 0 to 27% CD5− T cells in their blood. These are capable of cytotoxic and proliferative responses to alloantigens,23,24 and although CD5− T cells are associated with acute GvHD,19 it was hoped that there would be protective effects on the graft and sparing of the GvL effect that would outweigh the problems of GvHD. In addition, we attempted to increase the intensity of the conditioning regimen to increase both the immunosuppression and antileukemic effects of the therapy.
Mucosal B cells and their function
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Jo Spencer, Edward N. Janoff, Per Brandtzaeg
The Peyer's patch component of human GALT is constitutive in humans, as in mice. In humans, constitutive GALT, where clusters of B cells express CD5, can be observed in fetal intestine from around 18 weeks of gestation. Although used to identify the B-1 B-cell lineage in mice, CD5 can be expressed by immature transitional B cells in humans and can be an activation marker on human B cells (Figure 10.3). Indeed, fetal intestinal B cells are large activated cells, although there is no evidence of germinal center formation in the healthy fetal intestine. Like GALT in the postnatal intestine, B cells in fetal GALT infiltrate between the epithelial cells in the FAE, suggesting that recognition of microbial antigens is not required for this localization. However, results in originally germ-free then colonized rodents highlight the role of the microbiota in driving the magnitude of epithelial homing.
B Cells and Humoral Immunity
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
In mice, CD5+ cells produce mainly interleukin-10 and transforming growth factor-β, while CD5− cells secrete predominantly interleukin-6. These B cell subsets further differ with respect to antigen specificities, and Ig variable gene usage. CD5+ B cells are thought to have an important role in autoimmunity, and also frequently become malignant; more than 90% of chronic lymphocytic leukemias, and 60% of B cell lymphomas are CD5+. CD5+ cells are able to proliferate largely independently of antigen stimulation and T cell regulation. Interleukin-10 may play an autocrine role in this process. This may underlie the tendency toward the malignant phenotype in CD5+ cells.
Immunohistochemical and Immunocytochemical Analyses in Patients with Vitreoretinal Lymphoma
Published in Ocular Immunology and Inflammation, 2020
Satoru Kase, Kenichi Namba, Hiromi Kanno-Okada, Masahiro Onozawa, Daisuke Hidaka, Daiju Iwata, Kazuomi Mizuuchi, Takako Fukuhara, Junichi Fukuhara, Nobuyoshi Kitaichi, Yoshihiro Matsuno, Susumu Ishida
Cytological findings of all CB specimens showed relatively large atypical lymphoid cells with a high nuclear/cytoplasmic ratio and necrotic background (Figure 3A). All CB specimens also contained small lymphocytes and macrophages. CD3-positive lymphoma cells were not detected in any of the VRL cases. Immunoreactivity for CD5 was observed in one out of the nine VRL cases examined (11%) (Figure 3B). In contrast, immunoreactivity for CD20, a marker for B cells, was marked in the cell membrane of atypical lymphoid cells in 18 out of 19 eyes with VRL (95%). Reactive small lymphocytes did not show CD20 immunoreactivity (Figure 3C). CD10 immunoreactivity was not observed in the atypical lymphoid cells in 11 cases examined (Figure 3D). Nuclear immunoreactivity for Bcl-6 (Figure 3E) and MUM-1 (Figure 1F) was marked in five out of nine cases (56%) and eight out of nine cases (89%) examined, respectively. One VRL case was negative for Bcl-6, MUM-1, and CD10. Hematoxylin-eosin staining (HE) staining in a CB specimen (Figure 4A) and in a part of the subretinal space of an enucleated eye (Case 1) (Figure 4B) demonstrated similar findings regarding atypical cellular distribution and necrosis.
Clinicopathologic significance and therapeutic implication of de novo CD5+ diffuse large B-cell lymphoma
Published in Hematology, 2019
Huifen Tang, Hui Zhou, Juying Wei, Hui Liu, Wenbin Qian, Xiaohui Chen
De novo CD5+ DLBCL is a unique subset of DLBCL, and CD5 is a cell surface glycoprotein which is mainly expressed by T cells and a small subset of normal B cells. In general, CD5 is observed in the lymphoma cells of patients with CLL, MCL and Richter’s transformation of CLL [25]. In this study, we compared the clinicopathologic characteristics and prognosis of patients with CD5+ and CD5− DLBCL. We found that DLBCL patients with CD5 expression tended to be stage III-IV disease at diagnosis with a female preponderance. Furthermore, these patients were typically present with higher IPI scores (>2), bone marrow involvement, higher probability of >1 ECOG performance status, non-GCB, BCL2 overexpression, whereas seldom expressed CD10 or BCL6, and unconspicuous higher expression of Ki67. CD5 expression independently predicted significantly poorer OS and PFS in DLBCL.
Expression of BTK/p-BTK is different between CD5+ and CD5- B lymphocytes from Autoimmune Hemolytic Anemia/Evans syndromes
Published in Hematology, 2019
Ningning Duan, Manjun Zhao, Yi Wang, Yingying Qu, Hong Liu, Huaquan Wang, Limin Xing, Zonghong Shao
B lymphocytes can be divided into two subsets: CD5+ and CD5-B lymphocytes. Sen et al. [9] have suggested that the BCR signaling pathway has different effects in CD5+ and CD5-B lymphocytes. The activation of the BCR signaling pathway in CD5-B cells induces massive calcium mobilization and cell proliferation, while the activation of the BCR signaling pathway in CD5+B cells induces moderate intracellular calcium mobilization. Cells do not proliferate but undergo apoptosis. Presently, the expression of BTK on CD5+B lymphocytes in AIHA/ES patients was obviously higher than that of CLL patients and HCs, with the latter two groups displaying no significant difference. In addition, the expression of p-BTK on CD5+B lymphocytes in AIHA/ES patients was increased significantly by more than 70%. The increased number of CD5+B cells in the peripheral blood of patients with AIHA/ES may be due to the increased levels of BTK, especially the levels of p-BTK. Kil et al. [10] have reported that overexpression of BTK induced increased numbers of B1 cells in the spleen of mice, while the activation of BTK could alter the immune tolerance of CD5+B lymphocytes. Presently, the expression of BTK and p-BTK on clonal CD5+B lymphocytes in peripheral blood were not discernably different between CLL patients and HCs, but the expression of BTK and p-BTK on clonal CD5+B lymphocytes in CLL patients were obviously lower than that of AIHA/ES patients. We speculate that the effect of BTK on CD5+B cells in AIHA/ES patients differs from that of BTK on clonal CD5+B cells in CLL patients.