Do lymphocytes require calibration?

Abstract

Complexity in the activation/regulatory apparatus and the variable nature of the antigen-binding site dictate that B and T cells establish and select, during their development, appropriate activation and control mechanisms beyond simple antigen-binding specificity. These mechanisms are established partly by fixed interactions dictated by genetically defined structures, but they are also attained by calibration during ontogeny. This calibration depends on the ordered expression of early components (each of which is invariant), on their interaction with specific ligands, and on the receipt of invariant signals for calibration. Lymphocytes calibrate themselves by expressing various cell surface components, such as restricted heavy chain D-regions and pseudo-light chains. These are expressed in association with elements that will make up the antigen-receptor complex of mature lymphocytes. Calibration by invariant signals results in the establishment, selection and active maintenance of cellular activities which serve to control lymphocyte function. Since these cellular activities are one of a number of possible conditions, they are referred to as variant controls. Effectively calibrated basic cellular functions, specialized responses and cellular interactions allow lymphocytes to attain self-nonself discrimination. If calibration fails, lymphocytes will develop abnormalities, such as immunodeficiency and autoimmunity.