Beyond the CRAC: Diversification of ion signaling in B cells

Abstract

Ion channels act as critical gatekeepers, regulating the entry of ions such as sodium, calcium potassium, and magnesium into cells. While many are familiar with ion channels involved in the transport of calcium, and the important role of calcium as a second messenger in immune cell signaling, there are a multitude of ion channels, and together, they play a vital role in numerous metabolic and cellular processes. The importance of which is evidenced by the myriad of human disease pathologies associated with either ion deficiencies, or mutations in ion channel proteins, collectively referred to as channelopathies, and include both immunodeficiencies and autoimmune diseases. While the role of several ions and the interrogation of ion channels has been most extensively studied in the nervous system, we have also learned much about ion signaling and identified critical ion channels in T-cell biology; however, much less is known about ion signaling in B cells. Thus, this review is focused on the key role ions and ion channels and transporters play Abstract Although calcium signaling and the important role of calcium release-activated calcium channels is well recognized in the context of immune cell signaling, there is a vast diversity of ion channels and transporters that regulate the entry of ions beyond calcium, including magnesium, zinc, potassium, sodium, and chloride. These ions play a critical role in numerous metabolic and cellular processes. The importance of ions in human health and disease is illustrated by the identification of primary immunodeficiencies in patients with mutations in genes encoding ion channels and transporters, as well as the immunological defects observed in individuals with nutritional ion deficiencies. Despite progress in identifying the important role of ions in immune cell development and activation, we are still in the early stages of exploring the diversity of ion channels and transporters and mechanistically understanding the role of these ions in immune cell biology. Here, we review the biology of ion signaling in B cells and the identification of critical ion channels and transporters in B-cell development, activation, and differentiation into effector cells. Elucidating the role of ion channels and transporters in immune cell signaling is critical for expanding the repertoire of potential therapeutics for the treatment of immune disorders. Moreover, increased understanding of the role of ions in immune cell function will enhance our understanding of the potentially serious consequences of ion deficiencies in human health and disease. K E Y W O R D S calcium, CRAC, ion channels, magnesium, TRP, zincThis is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Integrative analyses identified ion channel genes GJB2 and SCNN1B as prognostic biomarkers and therapeutic targets for lung adenocarcinoma

“…A total of 328 ion channel genes were downloaded from HGNC database (http://www.genenames.org/) [19], including 26 Ca 2+ channel genes, 17 Cl − channel genes, 79 K + channel genes, 18 Na + channel genes, 22 gap junction protein families, 28 transient receptor potential (TRP) families. The detailed information was shown in Table S1.…”

Calcium-dependent signalling in B-cell lymphomas

“…Calcium channels in signalling . In addition to CRAC-Orai-STIM complexes, B cells express non-store-operated calcium channels [ 10 ]. While their role in Ca 2+ -dependent signalling pathways and in the differentiation of mammalian B-cells remains largely unknown, experiments involving the avian B-cell line (DT40) demonstrated that TRPC3 and TRPC7, two diacylglycerol-activated TRP channels, may contribute to BCR-induced influx of extracellular calcium [ 11 ].…”

Modulation of Adaptive Immunity and Viral Infections by Ion Channels

“…The lack of ORAI1 in B cells can lead to immunodeficiency and also to autoimmunity (Feske et al, 2012). However, the absence of ORAI1 does not affect B cell development (Mahtani and Treanor, 2019). Autoimmune disorders described in the absence of ORAI1 are associated with inflammation of the CNS (Gauthier et al, 2006;Feske et al, 2012).…”