Understanding B Cell Biology

AbstractAggressive, mature B-cell lymphomas represent a heterogeneous group of diseases including Burkitt Lymphoma (BL), High Grade B Cell Lymphomas (HGBL) (eg, Double-Hit B cell lymphomas (HGBL-DH: HGBL with MYC and BCL2 and/or BCL6 translocations)), HGBL, Not Otherwise Specified (HGBL, NOS) and Diffuse Large B Cell Lymphoma. The overlapping morphologic and immunohistochemical features of these lymphomas may pose diagnostic challenges in some cases, and a better understanding of potential diagnostic biomarkers and possible therapeutic targets is needed. Sphingosine 1 Phosphate Receptors (S1PR1-5) represent a family of G-protein coupled receptors that bind the sphingolipid (S1P) and influence migration and survival pathways in a variety of cell types, including lymphocytes. S1PRs are emerging as biomarkers in B cell biology and interaction between S1PR pathways and STAT3 or FOXP1 has been reported, especially in DLBCL. Our aim was to extend the understanding of the S1PR1, STAT3 and S1PR2, FOXP1 expression beyond DLBCL, into additional aggressive, mature B cell lymphomas such as BL, HGBL-DH and HGBL,NOS.Herein, we report that S1PR1 and S1PR2 showed different patterns of expression in mantle zones and follicle centers in reactive lymphoid tissue and, among the lymphomas in this study, Burkitt lymphomas showed a unique pattern of expression compared to HGBL and DLBCL. Additionally, we found that S1PR1 and S1PR2 expression was typically mutually exclusive and were expressed in a low proportion of cases (predominantly HGBL involving extranodal sites). Lastly, FOXP1 was expressed in a high proportion of the various case types and pSTAT3 was detected in a significant proportion of HGBL and DLBCL cases. Taken together, these findings provide further evidence that S1PR1, pSTAT3, S1PR2 and FOXP1 play a role in a subset of aggressive mature B cell lymphomas.

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Syndecan-1 and stromal heparan sulfate proteoglycans: key moderators of plasma cell biology and myeloma pathogenesis

Blood ◽

10.1182/blood.2020008188 ◽

2021 ◽

Author(s):

Zemin Ren ◽

Marcel Spaargaren ◽

Steven T Pals

Keyword(s):

Heparan Sulfate ◽

B Cell ◽

Plasma Cell ◽

Cell Biology ◽

Plasma Cells ◽

Specific Growth ◽

B Cell Development ◽

B Cell Antigen Receptor ◽

Growth And Survival ◽

Bm Niche

Plasma cells no longer express a B-cell-antigen-receptor and are hence deprived of signals crucial for survival throughout B-cell development. Instead, normal plasma cells, as well as their malignant myeloma counterparts, heavily rely on communication with the bone-marrow (BM) microenvironment for survival. The plasma cell heparan-sulfate-proteoglycan (HSPG) syndecan-1 (CD138), and HSPGs in the BM-microenvironment, acts as master regulator of this communication by co-opting specific growth- and survival-factors from the BM-niche. This designates syndecan-1/HSPGs, and their synthesis-machinery, as potential treatment targets in MM.

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The Role of B Cells in Adult and Paediatric Liver Injury

Frontiers in Immunology ◽

10.3389/fimmu.2021.729143 ◽

2021 ◽

Vol 12 ◽

Author(s):

Arzoo M. Patel ◽

Yuxin S. Liu ◽

Scott P. Davies ◽

Rachel M. Brown ◽

Deirdre A. Kelly ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

T Cell Activation ◽

Cell Biology ◽

Liver Diseases ◽

Cell Activation ◽

Persistent Inflammation ◽

Stage Disease ◽

End Stage ◽

The Impact

B lymphocytes are multitasking cells that direct the immune response by producing pro- or anti-inflammatory cytokines, by presenting processed antigen for T cell activation and co-stimulation, and by turning into antibody-secreting cells. These functions are important to control infection in the liver but can also exacerbate tissue damage and fibrosis as part of persistent inflammation that can lead to end stage disease requiring a transplant. In transplantation, immunosuppression increases the incidence of lymphoma and often this is of B cell origin. In this review we bring together information on liver B cell biology from different liver diseases, including alcohol-related and metabolic fatty liver disease, autoimmune hepatitis, primary biliary and primary sclerosing cholangitis, viral hepatitis and, in infants, biliary atresia. We also discuss the impact of B cell depletion therapy in the liver setting. Taken together, our analysis shows that B cells are important in the pathogenesis of liver diseases and that further research is necessary to fully characterise the human liver B cell compartment.

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Glucose-stimulated elevation of cytoplasmic calcium is defective in the diabetic Chinese hamster islet B cell

Acta Endocrinologica ◽

10.1530/eje.0.1340617 ◽

1996 ◽

Vol 134 (5) ◽

pp. 617-625 ◽

Cited By ~ 4

Author(s):

Per Lindström ◽

Janove Sehlin ◽

Barbara J Frankel

Keyword(s):

B Cell ◽

Insulin Release ◽

Cell Biology ◽

Glucose Utilization ◽

Islet Cells ◽

Insulin Response ◽

Chinese Hamster ◽

Cytoplasmic Calcium ◽

Essentially Normal ◽

Channel Agonist

Lindström P. Sehlin J, Frankel BJ. Glucose-stimulated elevation of cytoplasmic calcium is defective in the diabetic Chinese hamster islet B cell. Eur J Endocrinol 1996:134:617–25. ISSN 0804–4643 To characterize insulin release and cytoplasmic free Ca2+ [Ca2+]i) levels in the diabetic Chinese hamster islet B cell, islets from genetically normal subline M) and diabetic (subline L) hamsters were collagenase isolated. Insulin release and glucose utilization (conversion of D-[5-3H]glucose to 3H2O) were measured in whole islets; [Ca2+]i levels were measured in single islet cells using fura-2, The Ca2+ channel agonist, 12 mmol/l perchlorate, ClO4−, increased the subnormal insulin response during 20 mmol/l glucose perifusion, but did not normalize it. Glucose utilization measured over a 2-h period was normal. Glucose induced an initial decrease and then a rise in [Ca2+]i in 85% of the normal (presumably B) cells. In diabetic cells, the [Ca2+]i response was delayed, subnormal and only observed in 23% of the cells. When perchlorate or another Ca2+ channel agonist, 10 μmol/l CGP 28392, was added with glucose, a larger proportion of the diabetic cells (61–67%) showed increased [Ca2+]i and the mean [Ca2+]i response was not different from normal. However, neither perchlorate nor CGP 28392 could normalize glucose-stimulated insulin release, and K+-induced insulin release was decreased in diabetic islets. The K+ -induced [Ca2+]i rise was essentially normal in all the diabetic islet cells. Therefore, the diabetic hamster islet appears to metabolize glucose normally, but has a diminished insulin response to glucose and K+. The Ca2+ channel agonists markedly improve the subnormal [Ca2+]i response but not the insulin response. Glucose-induced elevation of [Ca2−]i and exocytosis appear defective in the diabetic Chinese hamster B cell. Per Lindström, Department of Histology and Cell Biology, Umea University, S-901 87 Umea, Sweden

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BAFF controls B cell metabolic fitness through a PKCβ- and Akt-dependent mechanism

Journal of Experimental Medicine ◽

10.1084/jem.20060990 ◽

2006 ◽

Vol 203 (11) ◽

pp. 2551-2562 ◽

Cited By ~ 138

Author(s):

Alina Patke ◽

Ingrid Mecklenbräuker ◽

Hediye Erdjument-Bromage ◽

Paul Tempst ◽

Alexander Tarakhovsky

Keyword(s):

B Cell ◽

Cell Biology ◽

Specific Protein ◽

Signaling Mechanism ◽

Kinase C ◽

B Cell Survival ◽

Cell Life ◽

Signaling Axis ◽

Metabolic Fitness ◽

Necrosis Factor

B cell life depends critically on the cytokine B cell–activating factor of the tumor necrosis factor family (BAFF). Lack of BAFF signaling leads to B cell death and immunodeficiency. Excessive BAFF signaling promotes lupus-like autoimmunity. Despite the great importance of BAFF to B cell biology, its signaling mechanism is not well characterized. We show that BAFF initiates signaling and transcriptional programs, which support B cell survival, metabolic fitness, and readiness for antigen-induced proliferation. We further identify a BAFF-specific protein kinase C β–Akt signaling axis, which provides a connection between BAFF and generic growth factor–induced cellular responses.

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