Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-07
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • B lymphocytes are found in blood lymph nodes spleen and

    2023-01-28

    B lymphocytes are found in blood, lymph nodes, spleen and tonsil and other mucosal tissues [110]. These cells originate in the bone marrow from a common progenitor shared with T, NK, and some DC subsets [111]. Progenitor Evaluation of Provider Prompts progress through the early stages of maturation, Evaluation of Provider Prompts rearranging heavy- and light-chain genes at the pro- to pre-B cell stage until they express rearranged IgM receptors on the cell surface as immature B cells, at which point they exit the bone marrow to continue maturation in the peripheral immune system [111]. Murine and human B cells have been shown to express all four types of adenosine receptors [112,113], as well as the presence of a complex network of ectoenzymes (nucleotidases, deaminases, kinases) and nucleoside transporters [114,115]. Recently, a review by Przybyła et al. [115] summarized the involvement of the adenosine system in the modulation of B cell functions, pointing out a critical role of adenosine in regulating the development, implantation and maintenance of the plasma cell population in bone marrow for the primary immune response as well as in orchestrating immunoglobulin class switching, a key mechanism of humoral immune response [115]. In particular, it has been observed that unactivated B cells are characterized by a high pericellular concentration of adenosine, whereas once activated these lymphocytes increase their ATP release [115]. The presence of this “ATPergic halo” protects activated B cells from the adenosine-induced inhibitory effect and exerts a proinflammatory role and a stimulatory effect on IgM production [115]. Interestingly, as observed with Treg cells, adenosine can regulate the function of Breg cells, a subset of immunosuppressive cells that support immunological tolerance [115]. In particular, Bregs were able to regulate both their own function and T cell activity via an adenosine signaling originating from the enzymatic degradation of ATP, released in the extracellular space from activated immune cells [116]. Indeed, it has been observed that Breg cells are endowed with CD39, CD73, CD25 but not CD26, thus allowing, in the presence of extracellular ATP, the production of adenosine by Bregs to a much larger extent than Tregs [116]. The biologic significance of this ability of B cells to produce adenosine can be appreciated in the context of their interactions with T cells [116]. Under resting condition, Breg cells promoted responses of activated T cells. On the other hand, once activated, Breg cells increase their ability to produce adenosine, becoming strongly suppressive toward T cells [116]. Of note, the ability of Breg cells to counteract T-cell functions depends on the state of their activation and to the microenvironmental context [116].
    Conclusions The research efforts of the last four decades have provided a large body of evidence regarding the involvement of adenosine signaling in shaping immune system activity. These studies paved the way to the introduction of both innovative anti-inflammatory tools, such as A3 receptor agonists and immune enhancing agents, such as immune checkpoint blockers in the oncology field (e.g., A2A receptor antagonists and CD73 blockers), some of which have already entered into the clinical arena with encouraging results either in terms of efficacy and safety. However, there are still significant gaps to fill in our understanding about the complex liaison occurring between the adenosine pathway and the immune system aimed to its optimal therapeutic exploitation.
    Introduction The purine nucleoside adenosine regulates many physiological and pathological processes via four G-protein coupled receptors (A1, A2A, A2B, A3) (Fredholm et al., 2005). These physiological processes range from regulation of transmitter release, in particular that of the major excitatory neurotransmitter, glutamate, to the induction of sleep following the gradual accumulation of adenosine during wakefulness (Basheer et al., 2004). In addition, the release of adenosine during a host of pathological events in the mammalian brain is believed to exert a strong neuroprotective influence via inhibition of glutamate release and neuronal and network activity, thereby reducing nutrient demand, as well as acting as a vasodilator during such insults as stroke, epileptic seizures and head injury (Cunha, 2005).