Definition and characteristics of autoantibodies

Natural autoantibodies (NAA) refer to immunoglobulins that are naturally produced and exist in normal bodies without active immunization with any antigens. NAA has the characteristics of multi-reactivity with antigen binding, and can recognize a variety of self and/or exogenous antigens. The existence of multi-reactivity does not mean that NAA completely lacks the specificity of antigen binding, and each autoreactive NAA has a unique set of specific target antigens. By analyzing the molecular structure of NAA, it is found that CDR3 is the main position to determine the multi-reactivity. For example, the heavy chain CDR3 of a polyclonal antibody can be transplanted into an IgG molecule that is originally mono-reactive, so that IgG can obtain multi-reactive activity.

Early literature showed that the binding of NAA to autoantigen has the characteristics of low affinity and high affinity. However, in recent years, it was found that the affinity of NAA changed greatly, and the dissociation constant was mostly in the range of10-5-10-8 m. It was found that the dissociation constant of NAA specific to IL-10-1α was as high as 5×/kloc-0. The network interaction between NAA with low affinity can produce new biological activities, which come from the comprehensive action of the network and are not necessarily possessed by the independent components that make up the network.

Connectivity is a concept used to describe the degree of reaction between antibody variable region (V region) and complementary Ig variable region or lymphocyte surface receptor variable region. NAA shows a higher correlation than the "immune" antibody produced by active immunization with foreign antigens. NAA can identify the idiotype of Ig in autologous serum, which can provide humoral immune system with the potential to establish a strong network mediated by V region. By binding to membrane surface antigen, NAA can activate B lymphocytes to regulate the functional state of the whole B cells, including the expression of NAA antibody. Normal IgG also has the important potential to select all T cell banks. Therefore, combining NAA plays a very important role in maintaining self-stability, especially in the homeostasis of immune system.

B cells can be divided into traditional CD5- B cells (B-2 cells), peritoneal CD5+ B cells (B- 1a cells) and peritoneal CD5-B cells (B- 1b cells) according to their location and surface markers. At present, most scholars believe that B- 1a cells are the main cells that produce NAA. B cells in human embryos mainly express self-reactive clones. At this time, CD5+ B cells constitute 50-70% of spleen B cells and 90% of cord blood and liver B cells. However, some data show that CD5- B cells can also produce multi-reactive NAA, and the number of CD5+ B cells in circulating blood of patients with rheumatoid arthritis and Sjogren's syndrome increases. These cells have been proved to produce pathological autoantibodies with high affinity, so the cytological basis of NAA production needs further study. The V region genes of human natural autoantibodies, monoclonal antibodies induced by foreign antigens and monoclonal antibodies related to autoimmune diseases were analyzed and studied, and some genetic structural characteristics of their respective antigen binding sites were found. Most NAA are encoded by germline genes, which will not mutate in fact, but the germline genes encoding NAA may encode pathological autoantibodies after somatic mutation.