Purinergic signalling in B cells

Abstract

Adenosine and adenosine triphosphate are involved in purinergic signaling which plays an important role in control of the immune system. Much data have been obtained regarding impact of purinergic signaling on dendritic cells, macrophages, monocytes and T lymphocytes, however less attention has been paid to purinergic regulation of B cells. This review summarizes present knowledge on ATP- and Ado-dependent signaling in B lymphocytes. Human B cells have been shown to express A-AR, A-AR, A-AR and A-AR and each subtype of P2 receptors. Surface of B cells exhibits two antagonistic ectoenzymatic pathways, one relies on constitutive secretion and resynthesis of ATP, while the second one depends on degradation of adenosine nucleotides to nucleosides and their subsequent degradation. Inactivated B cells remain under the suppressive impact of autocrine and paracrine Ado, whereas activated B lymphocytes increase ATP release and production. ATP protects B cells from Ado-induced suppression and exerts pro-inflammatory effect on the target tissues, and it is also involved in the IgM release. On the other hand, Ado synthesis is necessary for optimal development, implantation and maintenance of the plasmocyte population in bone marrow in the course of the primary immune response. Moreover, Ado plays an important role in immunoglobulin class switching, which is a key mechanism of humoral immune response. Disruption of purinergic signaling leads to severe disorders. Impairment of Ado metabolism is one of the factors responsible for common variable immunodeficiency. There are several lines of evidence that dysfunction of the immune system observed during diabetes may in part depend on disrupted ATP and Ado metabolism in the B cells.

Adenosine Signaling in Autoimmune Disorders

“…Due to their role in secreting antibodies and presenting antigens, B lymphocytes are the main actors in the humoral component of the adaptive immune system, and mature to plasma cells following the contact with specific antigens. The involvement of Ado signaling in the regulation of B lymphocyte functions has been well documented, starting from the demonstration that all four ARs are expressed by murine and human B cells, together with ecto-enzymes and membrane nucleoside transporters (for review see Reference [20]). In particular, it has been observed that inactivated B cells remain under the inhibitory effect of autocrine and paracrine Ado, whereas activated B cells increase ATP synthesis and release.…”

“…In particular, it has been observed that inactivated B cells remain under the inhibitory effect of autocrine and paracrine Ado, whereas activated B cells increase ATP synthesis and release. ATP in turn protects B cells from Ado-induced inhibition, exerts a pro-inflammatory effect on the target tissues, and stimulates IgM release [20]. On the other hand, studies on rodents showed that Ado synthesis is necessary for the development, implantation and maintenance of the plasma cell population in the bone marrow during the primary immune response.…”

Purinergic Signaling in Neutrophils During Inflammatory Diseases

“…Purinergic signaling system is a revolutionary selected system that can finetune the function of immune cells (1). In fact, purinergic signals mediated by P2R and P1R often play the opposite role in regulating the function of immune cells (9). Specifically, ATPmediated P2 receptor signal generally promotes the activation of immune cells, while ADOmediated P1R signal mainly limits the activation of immune cells (2,10).…”

Purinergic Receptors in Neurological Diseases With Motor Symptoms: Targets for Therapy

“…Gs/Gi protein activation, however, will work through the stimulation/inhibition of adenylate cyclase, respectively, with subsequent up- or down-regulation of cyclic AMP (cAMP) production. Final effects of purinergic receptor-promoted signaling will depend on the cell type and other intra-/inter-cellular conditions, as i.e., in physiological embryonic and adult neurogenesis (Oliveira et al, 2016 ), and in various pathological scenarios, such as inflammatory (Beamer et al, 2016 ; Madeira et al, 2017 ; Przybyła et al, 2018 ), oncological (Allard et al, 2016 ; Vijayan et al, 2017 ; Whiteside, 2017 ; Kazemi et al, 2018 ), neurological (Burnstock et al, 2011 ; Stockwell et al, 2017 ), metabolic (Lindberg et al, 2015 ; Csóka et al, 2017 ; Parpura et al, 2017 ; Tozzi and Novak, 2017 ; Labazi et al, 2018 ), psychiatric (Cunha, 2008 ; Lindberg et al, 2015 ; Ortiz et al, 2015 ; Krügel, 2016 ; Cheffer et al, 2017 ; Oliveros et al, 2017 ), cognitive (Illes and Verkhratsky, 2016 ), and peripheral neuromuscular and/or neuromotor diseases (Robitaille, 1995 ; Kalmar, 2005 ; Burnstock et al, 2013 ; Jiménez et al, 2014 ; Bogacheva and Balezina, 2015 ; Puchałowicz et al, 2015 ; Safarzadeh et al, 2016 ).…”