Chapter 9 Role of Intracellular pH in Lymphocyte Activation

Biochemical events associated with lymphocyte activation are initiated on the binding of ligand or lectin to the cell surface, leading to a cascade of signals transmitted from the membrane to the cell interior. Activation of certain pathways results in entry into the cell cycle while others prepare the cell for increased metabolic activity or maintain homeostasis. Lymphocyte activation has been shown to cause intracellular pH (pH i ), to either increase or decrease. The time course for altering pH i, is generally rapid, within 1-10 min, especially in T lymphocytes but may take 30-60 min in B lymphocytes stimulated with cytokines. Increased pH i most often results from the increased activity of the Na + /H + antiport. Increasing the activity of the antiport is not dependent on changes in [Ca 2+ ] i nor is it dependent on protein kinase C activity, though protein kinase C can activate the Na + /H + antiport in some settings. Decreased pH i occurs in mitogen- or antibody-stimulated human T lymphocytes. Decreased pH i requires an influx of extracellular Ca 2+. The changes in pH i that accompany lymphocyte activation may serve to modulate lymphocyte response to ligand or may be important for maintaining intracellular homeostasis in the face of increased metabolism.