**2. Overview of humoral immunity**

Antibodies are accumulated by the immune system to identify and neutralize foreign objects. They were the first specific product of the adaptive immune response to be identified and are found in the plasma, in the blood, and in extracellular fluids. Immunity mediated by antibodies is known as humoral immunity because of body fluids that were once known as humors [4]. The humoral immune response begins with the recognition of antigens by native B cells. These cells then undergo a process of clonal expansion and differentiation. In this way, the B cell matures into antibody-secreting plasma cells, which secrete antibodies. The activation of B cells and their differentiation into antibody-secreting plasma cells is triggered by antigen and usually requires helper T cells. The term "helper T cell" is often used to mean a cell from the TH2 class of CD4 T cells, but a subset of TH1 cells can also help in B-cell activation [5]. B cells can receive help from helper T cells when antigen bound by surface immunoglobulin is internalized and returned to the cell surface as peptides bound to major histocompatibility complex (MHC) class II molecules. MHC then delivers activating signals to the B cell. Thus, protein antigens binding to B cells both provide a specific signal to the B cell by cross-linking its antigen receptors and allow the B cell to attract antigen-specific T-cell help. These antigens are unable to induce antibody responses in animals or humans who lack T cells, and they are therefore known as thymus-dependent antigens [5]. The first signal required for B-cell activation is delivered through its antigen receptor. For thymus-dependent antigens, the second signal is delivered by a helper T cell that recognizes degraded fragments of the antigen as peptides bound to MHC class II molecules on the B-cell surface; the interaction between CD40 ligand on the T cell and CD40 on the B cell contributes an essential part of this second signal [5]. For thymus-independent antigens, the second signal can be delivered by the antigen itself or by non-thymus-derived accessory cells. The B-cell co-receptor complex of CD19:CD21:CD81 can greatly enhance B-cell responsiveness to antigen. CD21 (=complement receptor 2) is a receptor for the complement fragment C3d. Whether binding of CD21 enhances B-cell responsiveness by increasing B-cell signaling, by inducing co-stimulatory molecules on the B cell, or by increasing the receptor-mediated uptake of antigen is not yet known [5]. Antibodies are the effector products of humoral immunity. Finally, as this response declines, a pool of memory cells remains behind. If the body is reexposed to the antigen, these memory cells will recognize the antigen and respond much more quickly and effectively [6]. There are two purposes of antibodies. The first purpose is to neutralize the target threat, and the second purpose is to recruit other cells or proteins to an antigen so that those cells or proteins can eliminate the antigen [6]. AMR develops when recipient antibody is directed against donor human leukocyte antigens (HLA) on the endothelial layer of the allograft. Antibodies induce fixation and activation of the complement cascade, resulting in tissue injury. Complement and immunoglobulin are deposited within the allograft microvasculature, which results in an inflammatory process that is characterized by endothelial cell activation, upregulation of cytokines, infiltration of macrophages, increased vascular permeability, and microvascular thrombosis. This process ultimately manifests as allograft dysfunction [6].
