Members of the transient receptor potential (TRP) family of ion channels are cellular sensors involved in numerous physiological and pathological processes. We identified the TRP subfamily M member 7 (TRPM7) channel-kinase as a previously uncharacterized regulator of B cell activation. We showed that TRPM7 played a critical role in the early events of B cell activation through both its ion channel and kinase functions. DT40 B cells deficient in TRPM7 or expressing a kinase-deficient mutant of TRPM7 showed defective gathering of antigen and prolonged B cell receptor (BCR) signaling. We showed that lipid metabolism was altered in TRPM7-deficient cells and in cells expressing a kinase-deficient mutant of TRPM7 and suggest that PLC-γ2 may be a target of the kinase activity of TRPM7. Primary B cells that expressed less TRPM7 or were treated with a pharmacological inhibitor of TRPM7 also displayed defective antigen gathering and increased BCR signaling. Finally, we demonstrated that blocking TRPM7 function compromised antigen internalization and presentation to T cells. These data suggest that TRPM7 controls an essential process required for B cell affinity maturation and the production of high-affinity antibodies.

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.

Exposing students to interdisciplinary learning experiences has many benefits including a richer understanding of complex problems, promoting metacognition, and recognizing how to effectively use their skills. For biology students, immersion in creativity and design-thinking inherent to the arts can aid in their ability to imagine, innovate and communicate science. For art students who have been trained to develop unique visual vocabularies, an important learning experience would be to communicate didactic knowledge of an unfamiliar domain in a way that is visually compelling, imaginatively open-ended and informative. For both cohorts of students, academic training at the undergraduate level has remained somewhat sequestered in disciplinary silos. If we are to truly prepare students for careers in which they innovate, work collaboratively, solve problems and continue to learn, then we must provide authentic inquiry-based assignments that allow them to see the value of such proficiencies. This was the rationale behind designing this interdisciplinary assignment for biology and art students at the University of Toronto Scarborough. Here, we report on the design, implementation and insights from the pilot offering of this assignment. We hope that this provides a useful teaching tool for instructors interested in promoting interdisciplinary teaching and learning at the undergraduate level.