Purinergic signaling in B cells

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 A1-AR, A2A-AR, A2B-AR and A3-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.