scholarly journals Expression of the G-protein--coupled receptor BLR1 defines mature, recirculating B cells and a subset of T-helper memory cells

Blood ◽  
1994 ◽  
Vol 84 (3) ◽  
pp. 830-840 ◽  
Author(s):  
R Forster ◽  
T Emrich ◽  
E Kremmer ◽  
M Lipp
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cord Blood ◽  
G Protein ◽  
Blood Cells ◽  
Memory Cells ◽  
T Helper ◽  
G Protein Coupled Receptor ◽  
Color Flow ◽  
G Protein Coupled

The G-protein-coupled receptor BLR1 related to receptors for chemokines and neuropeptides has been identified as the first lymphocyte-specific member of the gene family characterized by seven transmembrane-spanning regions. Using a high-affinity anti-BLR1 monoclonal antibody (MoAb) and three-color flow cytometry it is shown that BLR1 expression on peripheral blood cells is limited to B cells and to a subset of CD4+ (14%) and CD8+ (2%) lymphocytes. T cells expressing BLR1 were positive for CD45R0, were negative for interleukin-2 receptors, show high levels of CD44, and show low levels of L-selectin. The majority of CD4+ cells originating from secondary lymphatic tissue, but none of cord blood- derived T cells, express BLR1. These observations suggest that BLR1 is a marker for memory T cells. Furthermore, BLR1 expression was detected on all CD19+ peripheral or tonsillar B lymphocytes, but only on a fraction of cord blood cells and bone marrow cells expressing CD19, sIgM, or sIgD. Interestingly, activation of both mature B and T cells by CD40 MoAb and CD3 MoAb, respectively, led to complete downregulation of BLR1. These data suggest that the G-protein-coupled receptor BLR1 is involved in functional control of mature recirculating B cells and T- helper memory cells participating in cell migration and cell activation.

scholarly journals Expression of the G-protein--coupled receptor BLR1 defines mature, recirculating B cells and a subset of T-helper memory cells

Blood ◽  
1994 ◽  
Vol 84 (3) ◽  
pp. 830-840 ◽  
Author(s):  
R Forster ◽  
T Emrich ◽  
E Kremmer ◽  
M Lipp
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cord Blood ◽  
G Protein ◽  
Blood Cells ◽  
Memory Cells ◽  
T Helper ◽  
G Protein Coupled Receptor ◽  
Color Flow ◽  
G Protein Coupled

Abstract The G-protein-coupled receptor BLR1 related to receptors for chemokines and neuropeptides has been identified as the first lymphocyte-specific member of the gene family characterized by seven transmembrane-spanning regions. Using a high-affinity anti-BLR1 monoclonal antibody (MoAb) and three-color flow cytometry it is shown that BLR1 expression on peripheral blood cells is limited to B cells and to a subset of CD4+ (14%) and CD8+ (2%) lymphocytes. T cells expressing BLR1 were positive for CD45R0, were negative for interleukin-2 receptors, show high levels of CD44, and show low levels of L-selectin. The majority of CD4+ cells originating from secondary lymphatic tissue, but none of cord blood- derived T cells, express BLR1. These observations suggest that BLR1 is a marker for memory T cells. Furthermore, BLR1 expression was detected on all CD19+ peripheral or tonsillar B lymphocytes, but only on a fraction of cord blood cells and bone marrow cells expressing CD19, sIgM, or sIgD. Interestingly, activation of both mature B and T cells by CD40 MoAb and CD3 MoAb, respectively, led to complete downregulation of BLR1. These data suggest that the G-protein-coupled receptor BLR1 is involved in functional control of mature recirculating B cells and T- helper memory cells participating in cell migration and cell activation.

scholarly journals A T-cell–redirecting bispecific G-protein–coupled receptor class 5 member D x CD3 antibody to treat multiple myeloma

Blood ◽  
2020 ◽  
Vol 135 (15) ◽  
pp. 1232-1243 ◽  
Author(s):  
Kodandaram Pillarisetti ◽  
Suzanne Edavettal ◽  
Mark Mendonça ◽  
Yingzhe Li ◽  
Mark Tornetta ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
T Cell ◽  
G Protein ◽  
T Cell Activation ◽  
Cell Activation ◽  
Plasma Cells ◽  
Phase 1 ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

Abstract T-cell–mediated approaches have shown promise in myeloma treatment. However, there are currently a limited number of specific myeloma antigens that can be targeted, and multiple myeloma (MM) remains an incurable disease. G-protein–coupled receptor class 5 member D (GPRC5D) is expressed in MM and smoldering MM patient plasma cells. Here, we demonstrate that GPRC5D protein is present on the surface of MM cells and describe JNJ-64407564, a GPRC5DxCD3 bispecific antibody that recruits CD3+ T cells to GPRC5D+ MM cells and induces killing of GPRC5D+ cells. In vitro, JNJ-64407564 induced specific cytotoxicity of GPRC5D+ cells with concomitant T-cell activation and also killed plasma cells in MM patient samples ex vivo. JNJ-64407564 can recruit T cells and induce tumor regression in GPRC5D+ MM murine models, which coincide with T-cell infiltration at the tumor site. This antibody is also able to induce cytotoxicity of patient primary MM cells from bone marrow, which is the natural site of this disease. GPRC5D is a promising surface antigen for MM immunotherapy, and JNJ-64407564 is currently being evaluated in a phase 1 clinical trial in patients with relapsed or refractory MM (NCT03399799).

scholarly journals Maturation of Lymphocyte Immunophenotypes and Memory T Helper Cell Differentiation During Development in Mice

2000 ◽  
Vol 8 (1) ◽  
pp. 47-60 ◽  
Author(s):  
Omar R. Fagoaga ◽  
Steven. M. Yellon ◽  
Sandra. L. Nehlsen-Cannarella
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cell Differentiation ◽  
B Cells ◽  
Cell Subset ◽  
T Helper Cell ◽  
Natural Killers ◽  
Memory Cells ◽  
Spleen Lymphocyte ◽  
T Helper

The goal of this study was to systematically investigate the ontogeny of lymphoid populations throughout postnatal development. In CD-1 mice, peak lymphocyte numbers occurred in blood on postnatal day 10 (dl0) including those for natural killers (NK1.1), B cells (CD19), T helper (CD3CD4), naïve T helper (CD4CD62LposCD44low), memory T helper (CD4CD62LnegCD44high), and T cytotoxic (CD3CD8) cells. As percent of total lymphocytes, peaks were achieved by d10 for all T helper subtypes but not B cells which declined to a nadir. In spleen, lymphocyte numbers increased exponentially after d10. Proportionately, NK and T cells peaked on d10, declined by d20, and increased 2–3-fold by d45. Naive T cells constituted the majority of lymphocytes during development while memory cells gained to 2.2% (blood) and 12 % (spleen) by d20. C57BL/6 mice had similar profiles except that the B cell nadir and T cell subset peaks were at d5. Peripheralization of critical numbers of lymphocytes by d10, and importantly, development of a repertoire of memory cells by d20, may define immune response capabilities that close the period of immaturity for the neonate.

scholarly journals Guidance of B Cells by the Orphan G Protein-Coupled Receptor EBI2 Shapes Humoral Immune Responses

Immunity ◽  
2009 ◽  
Vol 31 (2) ◽  
pp. 259-269 ◽  
Author(s):  
Dominique Gatto ◽  
Didrik Paus ◽  
Antony Basten ◽  
Charles R. Mackay ◽  
Robert Brink
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
G Protein ◽  
G Protein Coupled Receptor ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
G Protein Coupled

G Protein Coupled Receptor Kinase 3 (GRK3) - Deficient T Cells Demonstrate Enhanced Migration To CXCL12 And CX3CL1

2011 ◽  
Vol 127 (2) ◽  
pp. AB166-AB166
Author(s):  
L.R. Rothlein ◽  
R.G. Timoshchenko ◽  
D.J. Fitzhugh ◽  
M.W. McGinnis ◽  
G. Laroche ◽  
...  
Keyword(s):  
T Cells ◽  
G Protein ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals G Protein-Coupled Receptor 83 Overexpression in Naive CD4+CD25− T Cells Leads to the Induction of Foxp3+ Regulatory T Cells In Vivo

2006 ◽  
Vol 177 (1) ◽  
pp. 209-215 ◽  
Author(s):  
Wiebke Hansen ◽  
Karin Loser ◽  
Astrid M. Westendorf ◽  
Dunja Bruder ◽  
Susanne Pfoertner ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
G Protein ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals Identification of a Gene Induced by Glucocorticoids in Murine T-Cells: A Potential G Protein-Coupled Receptor

1991 ◽  
Vol 5 (9) ◽  
pp. 1331-1338 ◽  
Author(s):  
Maureen T. Harrigan ◽  
N. Faith Campbell ◽  
Suzanne Bourgeois
Keyword(s):  
T Cells ◽  
G Protein ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

Predictive value of circulating B cells and T cell subsets in melanoma patients treated with neoadjuvant ipilimumab and interferon.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15036-e15036
Author(s):  
Arjun Khunger ◽  
Ghanashyam Sarikonda ◽  
Jenn Tsau ◽  
Zeni Alfonso ◽  
Jane Gao ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Peripheral Blood ◽  
Post Treatment ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Memory Cells ◽  
Color Flow ◽  
Time Points ◽  
Effector Memory Cells

e15036 Background: Patients with locally/regionally advanced melanoma were treated on a clinical trial with a neoadjuvant combination of ipilimumab (ipi) and high dose IFNα2b (HDI) (Tarhini et al, JITC 2018). In this study, immune cell composition in peripheral blood samples collected at various time points was measured to determine any correlation with clinical outcomes and investigate the immune modulating effect of the combination therapy. Methods: Patients were randomized to neoadjuvant ipi at 3 mg/kg or 10 mg/kg, both given in combination with HDI. Tumor radiologic responses were designated as complete (CR), partial (PR), stable disease (SD) or disease progression (PD). Pathologic complete response (pCR) was defined as absence of viable tumor on histologic assessment. Peripheral blood mononuclear cells (PBMC) from treated patients (N = 28) were tested at baseline (before initiating ipi-HDI), then at 6-weeks, 3-months and 12-months (following neoadjuvant ipi-HDI). High complexity (14-color) flow cytometry analysis was performed to detect key immunological biomarkers including myeloid derived suppressor cells (MDSCs), B cells, regulatory T cells (Tregs), PD-1 and TIM3 expression on T-cells, and differentiation of T-cells into Th1, Th2 or Th17 phenotype at different time points during systemic immunotherapy. Statistical significance was determined using R-package employing Kruskal’s test. Results: Lower levels of peripheral Tregs (p = 0.02), MDSCs (p = 0.05), and CD4 effector memory cells (p = 0.04) at 3-months post treatment correlated with radiologic response. In addition, lower change from baseline at 3 months in CD4/CD8 ratio (p = 0.04), levels of Tregs (p = 0.01) and CD4 effector memory cells (p = 0.02) was associated with radiologic response. Patients exhibiting pCR had significantly lower Tregs (p = 0.04) at 6-months post treatment and significantly higher CD8 central memory cells at both 3 months (p = 0.04) and 12 month time-points (p = 0.01) as compared to patients without pCR. Finally, patients without pCR had significantly lower change from baseline in CD19 B cells at 6 months (p = 0.01) and 12 months (p = 0.04) as compared to patients with pCR. Conclusions: Our data demonstrates that the levels of immunosuppressive cells including Tregs and MDSCs in periphery are negatively associated with response. Higher levels of CD8 memory cells and B cells on-treatment are associated with clinical benefit.

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