Self and Nonself Recognition by Coreceptors on B Lymphocytes: Regulation of B Lymphocytes by CD19, CD21, CD22, and CD72
B-cell antigen receptor (BCR) signaling plays an essential role in regulation of the development and function of B lymphocytes (see Chapter 4). These signals are modulated by coreceptors expressed on the surface of B cells, including CD19, CD21 (complement receptor 2, CR2), CD22, CD72 (Lyb-2), and low-affinity receptor for IgG (FcγRII) (see Chapter 6 on Fc receptors). When CD19/CD21 complex is colligated with BCR, this complex positively regulates BCR signaling through the recruitment of signaling molecules, such as a phosphatidylinositol 3-kinase (PI3K), to their phosphorylated tyrosines. On the other hand, CD22 and CD72 negatively regulate BCR signaling through the recruitment of the SH2-domain-containing protein tyrosine phosphatase-1 (SHP-1) to their phosphorylated immunoreceptor tyrosine-based inhibitory motifs (ITIMs). From the characterization of each of these coreceptors deficient mice, now it is clear that the regulations by these coreceptors physiologically play a significant role in the development, activation, proliferation and differentiation of B cells. Importantly, these coreceptors are able to detect and respond to extracellular environment and modulate BCR signaling by their ligand bindings. These functions contribute to the recognition of self- and nonself-antigens (Ags), in some cases, in cooperation with the innate immune system, such as the recognition of activated complement fragments by CD21 (see Chapter 1 on innate immunity). In this chapter, we focus on the physiological function of the CD19, CD21, CD22, and CD72 and their molecular mechanisms involving signal transduction by these coreceptors, which will help us to understand how B cells recognize self and nonself.
KeywordsSialic Acid Complement Receptor Sialic Acid Recognition Semaphorin CD100
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