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Douglas T. Fearon
Wellcome Trust Immunology Unit
University of Cambridge School of Clinical Medicine
Cambridge, UK

Non-Structural Determinants of Immunogenicity and CD19, CD21, and CD22 of B Lymphocytes

The immunogenicity of an antigen is determined not only by its structure, which governs interactions with antigen receptors of lymphocytes and MHC class I and II proteins of antigen presenting cells, but also by its biological characteristics. Three receptors of the B lymphocyte evaluate these latter aspects of antigen, CD19, CD21, and CD22. CD19 and CD21 form a complex that costimulates the B lymphocyte when coligated with mIg. Such coligation can occur with antigen to which C3d of complement has covalently bound, which enables the B cell to evaluate the possible microbial origin of an antigen. CD22 recruits the phosphotyrosine phosphatase SHP-1 and, when juxtaposed to mIg, is a suppressor of signaling. Conversely, sequesration of CD22 from mIg by ligands on surrounding B cells enhances signaling, permitting B cells in secondary lymphoid organs to have lower thresholds for simulation. Thus, B cells bias their response toward antigens of microbial origin that are encountered in lympboid organs.

During the germinal center reaction, the functions of these two coreceptor systems are altered to facilitate B cell activation. The intracellular concentration of SHP-1 is downregulated in centroblasts and centrocytes to approximately 10% that of mantle zone B cells, and follicular dendritic cells (FDCs) of the germinal center express a ligand for CD19. Therefore, centrocytes are simultaneously released from the inhibitory effects of CD22 and costimulated by CD19, indicating that once commitment to a T-dependent humoral immune response has occurred, the activities of the coreceptors are modified to create an optimal state for cellular activation.