During an active immune response (a,c), the apparent affinity increases, as reflected by a decreased average standard chemical potential, and changes in clonal composition alter the limiting coefficient. regulates the removal of our own molecules and cells once these are losing function due to ageing, attrition, or contamination. It maintains a healthy balance with the myriad of microbes and viruses present in our bodies [1]. To carry out these functions, the system utilizes an intricate regulatory mechanism that tunes its potential for destruction over a very wide range [2,3]. The humoral adaptive immune system consists of cells (B cells) and soluble molecules (antibodies) and has the remarkable ability to generate an immensely diverse repertoire of its element by adjusting, amongst others, one critical factor of molecular interactions: affinity [4,5]. Together with albumin and other macromolecules antibodies, (Ab) creates a molecularly crowded environment in blood, where molecules are in constant interaction with each other. Because of the huge structural diversity of antibody binding sites, these interactions in the blood, and with all molecules IL1A and cells contacted by blood, the strength of binding interactions also spans a huge range. In this article Galactose 1-phosphate Potassium salt we expand a conceptual framework, based on physics and B-cell differentiation, for the distribution and organization of antibody interactions, and argue that a recently developed quantitative serology technology is suitable for characterizing the proposed model. == 2. Immunological and Physical Rules of the System: B Cells as Sensors and Effectors == Antibodies are present in three main forms in blood: as part of a receptor complex, the B-cell antigen receptor (BCR) or membrane immunoglobulin (mIg), with cellular signaling capacity [6,7,8]; in secreted, freely circulating form (this is what we usually refer to as serum antibodies) [9,10], and in receptor-bound form, attached to the immunoglobulin Fc receptors of cells [11,12,13]. The last form is responsible for effector functions and is not dealt with in this article but is also important in quantitative modeling of antibody homeostasis. Based on the form of antibody they express, there are three categories of B cells: (1) resting nave B2 lymphocytes and memory B cells (MBC) display BCR but do not secrete Abs; (2) activated B1 cells, pre-plasmablasts, lymphoblasts express both surface and secreted Ab; (3) plasma cells, such as short-lived plasma cells (SLPC) and long-lived plasma cells (LLPC), only secrete antibodies. The second and third group together is also called antibody secreting cells (ASC). In accordance with these categories, these cell types function as antigen (Ag) sensors, as both sensors and effectors and as effectors only (Physique 1). A feedback mechanism based on antigen concentration and antibody engagement operates to generate sensors and effectors against all potential targets [8]. In short, the extent of antigen binding to BCR determines cell survival via signals delivered through the BCR [6]. Too much or too little BCR engagement leads to cell death, while the proper extent of BCR engagement initiates cell activation or cell survival. Activated B cells become lymphoblasts, with the ability to secrete antibody and yet depend on BCR signals for survival [14,15,16]. Terminally differentiated antigen secreting cells, plasma cells, do not depend on BCR signals [17,18,19] but produce secreted antibodies, which in turn reduce the concentration of target antigen [20]. As antigen is Galactose 1-phosphate Potassium salt usually cleared the immune response retracts, short-lived effector cells (SLPC) die, and a new steady state equilibrium is established. Affinity maturation of antibodies changes the concentration of antigen required for a given extent of antibody engagement, therefore resulting in memory cells capable of more sensitive detection (sensor MBC) or more effective removal (LLPC) of antigen [20]. The new equilibrium allows MBC with increased sensitivity to survive, backing up the front line of secreted antibodies. Cycles of these events shape the Galactose 1-phosphate Potassium salt lymphocyte repertoire and the theoretical space of all antibody interactions. == Physique 1. == Categorization of antibodies based on sensor and effector function. The Galactose 1-phosphate Potassium salt two functional types of antibodies, two corresponding cell types and the mixed type are shown. BCR, B-cell receptor. == 3. The Configuration Space of Serum Antibodies == From the medical and biological perspective, the humoral immune response takes place in various anatomical locations of the host: lymph nodes, spleen, bone marrow, blood, or periphery. The specialized structure of these tissues contributes to the development, differentiation and activation of B-cells and antibody secreting cells [4,21,22]. Nevertheless, all these tissues are physically connected, and while cell trafficking is usually regulated.
