Role of class IA phosphoinositide 3-kinase in B lymphocyte development and functions

2004 ◽  
Vol 32 (2) ◽  
pp. 320-325 ◽  
Author(s):  
S. Koyasu
Keyword(s):  
B Lymphocyte ◽  
Cell Types ◽  
Lymphocyte Development ◽  
Regulatory Subunits ◽  
B Lymphocyte Development ◽  
Intracellular Organelles ◽  
B Lineage ◽  
Phosphoinositide 3 Kinase

PI3K (phosphoinositide 3-kinase) family members control a variety of cellular responses, such as cell growth, survival, cytoskeletal remodelling and the trafficking of intracellular organelles, in many cell types, including lymphocytes. It has been difficult to evaluate the roles of distinct PI3Ks in immune responses, because specific inhibitors for each PI3K are lacking and most stimuli activate multiple PI3Ks. The development of gene-targeted mice has now allowed the elucidation of roles played in vivo by PI3K species in the immune system. Studies on mice deficient in catalytic as well as regulatory subunits of class IA PI3Ks have shown the importance of this class of PI3K in B lineage cells. Here I discuss the role of class IA PI3Ks in B lymphocyte development and B cell antigen receptor-mediated signal transduction.

scholarly journals Flow cytometric analysis of human bone marrow. II. Normal B lymphocyte development

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1316-1324 ◽  
Author(s):  
MR Loken ◽  
VO Shah ◽  
KL Dattilio ◽  
CI Civin
Keyword(s):  
Bone Marrow ◽  
Cell Surface ◽  
B Lymphocyte ◽  
Human Bone ◽  
Lymphocyte Development ◽  
Hla Dq ◽  
B Lymphocyte Development ◽  
B Lineage ◽  
B Lymphoid ◽  
B Lineage Cells

Abstract A panel of B lymphoid-reactive monoclonal antibodies was used to analyze the phenotypic changes that accompany B lymphocyte development in normal human bone marrow. The B lymphoid cells were identified using light scattering and the expression of CD19 on a flow cytometer. Quantitative three-color immunofluorescence was then used to correlate other cell surface antigens on these cells identified as B lymphoid in normal marrow. CD10 and CD20 identified almost exclusive populations and provided a convenient means of discriminating between the less and more mature B lineage cells. The CD10+ cells could be further subdivided using CD34. The population of CD19+, CD10+, CD34+ cells comprised only 0.6% of marrow cells, but these contained the majority of terminal deoxynucleotidyl transferase (TdT+) cells. In the assessment of class II antigens, HLA-DR was expressed on all B lineage cells whereas HLA-DP preceded HLA-DQ in appearance during the developmental process. Among the later antigens expressed on B lineage cells, cell surface IgM, CD20, and HLA-DQ were expressed at essentially the same time. Cell surface CD10 was lost at the time when CD21 and CD22 were acquired on the cell surface. These data illustrate that multiparameter flow cytometry can be used to define a continuous progression of stages of B lymphocyte development based on cell surface antigen expression even though these cells represent a minor fraction of normal marrow cells.

scholarly journals Regulation of B Lymphocyte Development by Histone H2A Deubiquitinase BAP1

2021 ◽  
Vol 12 ◽  
Author(s):  
Yun Hsiao Lin ◽  
Yue Liang ◽  
HanChen Wang ◽  
Lin Tze Tung ◽  
Michael Förster ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Cycle Progression ◽  
B Lymphocyte ◽  
Cell Development ◽  
B Cell Development ◽  
Lymphocyte Development ◽  
A Cell ◽  
B Lymphocyte Development

BAP1 is a deubiquitinase (DUB) of the Ubiquitin C-terminal Hydrolase (UCH) family that regulates gene expression and other cellular processes, via deubiquitination of histone H2AK119ub and other substrates. BAP1 is an important tumor suppressor in human, expressed and functional across many cell-types and tissues, including those of the immune system. B lymphocytes are the mediators of humoral immune response, however the role of BAP1 in B cell development and physiology remains poorly understood. Here we characterize a mouse line with a selective deletion of BAP1 within the B cell lineage (Bap1fl/fl mb1-Cre) and establish a cell intrinsic role of BAP1 in the regulation of B cell development. We demonstrate a depletion of large pre-B cells, transitional B cells, and mature B cells in Bap1fl/fl mb1-Cre mice. We characterize broad transcriptional changes in BAP1-deficient pre-B cells, map BAP1 binding across the genome, and analyze the effects of BAP1-loss on histone H2AK119ub levels and distribution. Overall, our work establishes a cell intrinsic role of BAP1 in B lymphocyte development, and suggests its contribution to the regulation of the transcriptional programs of cell cycle progression, via the deubiquitination of histone H2AK119ub.

scholarly journals Lymphocyte cell motility: the twisting, turning tale of phosphoinositide 3-kinase

2007 ◽  
Vol 35 (5) ◽  
pp. 1109-1113 ◽  
Author(s):  
J.S. Oak ◽  
M.P. Matheu ◽  
I. Parker ◽  
M.D. Cahalan ◽  
D.A. Fruman
Keyword(s):  
Cell Motility ◽  
Cell Types ◽  
Lymphocyte Migration ◽  
Regulatory Subunits ◽  
Lipid Kinases ◽  
Cell Type Specific ◽  
Phosphoinositide 3 Kinase ◽  
Lymphocyte Motility

The PI3K (phosphoinositide 3-kinase) family of lipid kinases regulate cell motility in diverse organisms and cell types. In mammals, the main PI3K enzyme activated by chemokine receptor signalling is the class IB isoform, p110γ. Studies of p110γ-knockout mice have shown an essential function for this isoform in chemotaxis of neutrophils and macrophages both in vitro and in vivo. However, the roles of p110γ and other PI3K enzymes and regulatory subunits in lymphocyte motility have been more difficult to discern. Recent studies of adoptively transferred, fluorescently labelled lymphocytes have revealed complex and unexpected functions for PI3K in lymphocyte migration in vivo. In this review we highlight cell-type-specific roles for PI3K catalytic and regulatory subunits in the homing and basal motility of lymphocytes in the intact lymph node.

The role of nicotinic receptors in B-lymphocyte development and activation

Life Sciences ◽  
2007 ◽  
Vol 80 (24-25) ◽  
pp. 2334-2336 ◽  
Author(s):  
M.V. Skok ◽  
R. Grailhe ◽  
F. Agenes ◽  
J.-P. Changeux
Keyword(s):  
Nicotinic Receptors ◽  
B Lymphocyte ◽  
Lymphocyte Development ◽  
B Lymphocyte Development

scholarly journals Flow cytometric analysis of human bone marrow. II. Normal B lymphocyte development

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1316-1324 ◽  
Author(s):  
MR Loken ◽  
VO Shah ◽  
KL Dattilio ◽  
CI Civin
Keyword(s):  
Bone Marrow ◽  
Cell Surface ◽  
B Lymphocyte ◽  
Human Bone ◽  
Lymphocyte Development ◽  
Hla Dq ◽  
B Lymphocyte Development ◽  
B Lineage ◽  
B Lymphoid ◽  
B Lineage Cells

A panel of B lymphoid-reactive monoclonal antibodies was used to analyze the phenotypic changes that accompany B lymphocyte development in normal human bone marrow. The B lymphoid cells were identified using light scattering and the expression of CD19 on a flow cytometer. Quantitative three-color immunofluorescence was then used to correlate other cell surface antigens on these cells identified as B lymphoid in normal marrow. CD10 and CD20 identified almost exclusive populations and provided a convenient means of discriminating between the less and more mature B lineage cells. The CD10+ cells could be further subdivided using CD34. The population of CD19+, CD10+, CD34+ cells comprised only 0.6% of marrow cells, but these contained the majority of terminal deoxynucleotidyl transferase (TdT+) cells. In the assessment of class II antigens, HLA-DR was expressed on all B lineage cells whereas HLA-DP preceded HLA-DQ in appearance during the developmental process. Among the later antigens expressed on B lineage cells, cell surface IgM, CD20, and HLA-DQ were expressed at essentially the same time. Cell surface CD10 was lost at the time when CD21 and CD22 were acquired on the cell surface. These data illustrate that multiparameter flow cytometry can be used to define a continuous progression of stages of B lymphocyte development based on cell surface antigen expression even though these cells represent a minor fraction of normal marrow cells.

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