IDENTIFICATION AND ROLE OF HUMAN REGULATORY B LYMPHOCYTES IN CHRONIC LYMPHOCYTIC LEUKEMIA
(Abstract release date: 05/19/16)
EHA Library. Audrey M. 06/09/16; 134683; PB1783
Mrs. Mohr Audrey
Contributions
Contributions
Abstract
Abstract: PB1783
Type: Publication Only
Background
Chronic lymphocytic leukemia (CLL) is the most common leukemia in Europe. There is no curative treatment. CLL is characterized by expansion of CD19+ CD5+ B cells in blood, lymph nodes and bones marrow. In this pathology, immune responses are disrupted, at least due to dysfunctions of T cells, contributing to the immunodeficiency and the disease progression. Generally speaking, B lymphocytes play an intricate role in the immune system and are able to slowdown the anti-tumor responses favoring tumor escape. They are called regulatory B cells.
Aims
The main focus of this project is to evaluate the regulatory function of CLL B cells, aiming to estimate their influence on the lack of anti-tumor responses mediated by T cells.
Methods
In vitro models of co-cultures between T and B cells are used to appraise the regulatory capacity of CLL B cells on T cell proliferation evaluated by flow cytometry. Regulatory activity of CLL B cells, stimulated or not with CpG-ODN, is estimated as their ability to inhibit the T cell proliferation. Concurrently, phenotypic characteristics of regulatory B cells and T cells are evaluated.
Results
Two groups of patients have been identified following CpG-ODN stimulation. The first group presents defective regulatory B cell functions compared with control B cells. In the second group, no inhibitory activity is detected, leading even to T cell proliferation in some cases. Compared with unstimulated cells, stimulation with CpG-ODN do not induce any regulation, suggesting insensitivity of the second group. Surprisingly, the level of TLR9 expression is similar in both groups. Furthermore, no correlation is found between functional and phenotypic signature of T and B cells. However longitudinal study suggests a switch of group with a strong clinical course.
Conclusion
These results suggest functional TLR9 pathway but alteration of the regulatory-induced function of CLL B cells in the first group, while the TLR9 pathway seems to be totally defective in the second group of patients, explaining the lack of regulation. To go further, it will be of interest to identify the molecular mechanisms damaging the TLR9 pathway. These results would contribute to clarify the lack of anti-tumor immune response found in the CLL patients.
Session topic: E-poster
Keyword(s): B cell chronic lymphocytic leukemia, Regulatory
Type: Publication Only
Background
Chronic lymphocytic leukemia (CLL) is the most common leukemia in Europe. There is no curative treatment. CLL is characterized by expansion of CD19+ CD5+ B cells in blood, lymph nodes and bones marrow. In this pathology, immune responses are disrupted, at least due to dysfunctions of T cells, contributing to the immunodeficiency and the disease progression. Generally speaking, B lymphocytes play an intricate role in the immune system and are able to slowdown the anti-tumor responses favoring tumor escape. They are called regulatory B cells.
Aims
The main focus of this project is to evaluate the regulatory function of CLL B cells, aiming to estimate their influence on the lack of anti-tumor responses mediated by T cells.
Methods
In vitro models of co-cultures between T and B cells are used to appraise the regulatory capacity of CLL B cells on T cell proliferation evaluated by flow cytometry. Regulatory activity of CLL B cells, stimulated or not with CpG-ODN, is estimated as their ability to inhibit the T cell proliferation. Concurrently, phenotypic characteristics of regulatory B cells and T cells are evaluated.
Results
Two groups of patients have been identified following CpG-ODN stimulation. The first group presents defective regulatory B cell functions compared with control B cells. In the second group, no inhibitory activity is detected, leading even to T cell proliferation in some cases. Compared with unstimulated cells, stimulation with CpG-ODN do not induce any regulation, suggesting insensitivity of the second group. Surprisingly, the level of TLR9 expression is similar in both groups. Furthermore, no correlation is found between functional and phenotypic signature of T and B cells. However longitudinal study suggests a switch of group with a strong clinical course.
Conclusion
These results suggest functional TLR9 pathway but alteration of the regulatory-induced function of CLL B cells in the first group, while the TLR9 pathway seems to be totally defective in the second group of patients, explaining the lack of regulation. To go further, it will be of interest to identify the molecular mechanisms damaging the TLR9 pathway. These results would contribute to clarify the lack of anti-tumor immune response found in the CLL patients.
Session topic: E-poster
Keyword(s): B cell chronic lymphocytic leukemia, Regulatory
Abstract: PB1783
Type: Publication Only
Background
Chronic lymphocytic leukemia (CLL) is the most common leukemia in Europe. There is no curative treatment. CLL is characterized by expansion of CD19+ CD5+ B cells in blood, lymph nodes and bones marrow. In this pathology, immune responses are disrupted, at least due to dysfunctions of T cells, contributing to the immunodeficiency and the disease progression. Generally speaking, B lymphocytes play an intricate role in the immune system and are able to slowdown the anti-tumor responses favoring tumor escape. They are called regulatory B cells.
Aims
The main focus of this project is to evaluate the regulatory function of CLL B cells, aiming to estimate their influence on the lack of anti-tumor responses mediated by T cells.
Methods
In vitro models of co-cultures between T and B cells are used to appraise the regulatory capacity of CLL B cells on T cell proliferation evaluated by flow cytometry. Regulatory activity of CLL B cells, stimulated or not with CpG-ODN, is estimated as their ability to inhibit the T cell proliferation. Concurrently, phenotypic characteristics of regulatory B cells and T cells are evaluated.
Results
Two groups of patients have been identified following CpG-ODN stimulation. The first group presents defective regulatory B cell functions compared with control B cells. In the second group, no inhibitory activity is detected, leading even to T cell proliferation in some cases. Compared with unstimulated cells, stimulation with CpG-ODN do not induce any regulation, suggesting insensitivity of the second group. Surprisingly, the level of TLR9 expression is similar in both groups. Furthermore, no correlation is found between functional and phenotypic signature of T and B cells. However longitudinal study suggests a switch of group with a strong clinical course.
Conclusion
These results suggest functional TLR9 pathway but alteration of the regulatory-induced function of CLL B cells in the first group, while the TLR9 pathway seems to be totally defective in the second group of patients, explaining the lack of regulation. To go further, it will be of interest to identify the molecular mechanisms damaging the TLR9 pathway. These results would contribute to clarify the lack of anti-tumor immune response found in the CLL patients.
Session topic: E-poster
Keyword(s): B cell chronic lymphocytic leukemia, Regulatory
Type: Publication Only
Background
Chronic lymphocytic leukemia (CLL) is the most common leukemia in Europe. There is no curative treatment. CLL is characterized by expansion of CD19+ CD5+ B cells in blood, lymph nodes and bones marrow. In this pathology, immune responses are disrupted, at least due to dysfunctions of T cells, contributing to the immunodeficiency and the disease progression. Generally speaking, B lymphocytes play an intricate role in the immune system and are able to slowdown the anti-tumor responses favoring tumor escape. They are called regulatory B cells.
Aims
The main focus of this project is to evaluate the regulatory function of CLL B cells, aiming to estimate their influence on the lack of anti-tumor responses mediated by T cells.
Methods
In vitro models of co-cultures between T and B cells are used to appraise the regulatory capacity of CLL B cells on T cell proliferation evaluated by flow cytometry. Regulatory activity of CLL B cells, stimulated or not with CpG-ODN, is estimated as their ability to inhibit the T cell proliferation. Concurrently, phenotypic characteristics of regulatory B cells and T cells are evaluated.
Results
Two groups of patients have been identified following CpG-ODN stimulation. The first group presents defective regulatory B cell functions compared with control B cells. In the second group, no inhibitory activity is detected, leading even to T cell proliferation in some cases. Compared with unstimulated cells, stimulation with CpG-ODN do not induce any regulation, suggesting insensitivity of the second group. Surprisingly, the level of TLR9 expression is similar in both groups. Furthermore, no correlation is found between functional and phenotypic signature of T and B cells. However longitudinal study suggests a switch of group with a strong clinical course.
Conclusion
These results suggest functional TLR9 pathway but alteration of the regulatory-induced function of CLL B cells in the first group, while the TLR9 pathway seems to be totally defective in the second group of patients, explaining the lack of regulation. To go further, it will be of interest to identify the molecular mechanisms damaging the TLR9 pathway. These results would contribute to clarify the lack of anti-tumor immune response found in the CLL patients.
Session topic: E-poster
Keyword(s): B cell chronic lymphocytic leukemia, Regulatory
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