Chapter 12 - Regulation of Antigen Receptor Signaling by the Co-Receptors, CD19 and CD22

Abstract

The chapter discusses the regulation of antigen receptor signaling by the co-receptors. Membrane immunoglobulin (mIg), the antigen receptor on B cells, is a central regulator of B cell fate. Antigen binding to mIg triggers signaling pathways, such as calcium ions mobilization or MAP kinase activation. These signals may induce proliferation, differentiation, or functional inactivation and apoptosis, depending on the cellular context and microenvironment. B cells constitutively express a set of inhibitory receptors that are regulated by surprisingly different mechanisms. In most cases, inhibition relies on the presence of immuno-receptor tyrosine inhibition motif (ITIM) motifs and on the recruitment of either SHP-1 or SHIP. Some receptors are constitutively tyrosine phosphorylated (CD72, PIR-B) and in others tyrosine phosphorylation is induced (CD22, FcγRII). The crucial regulation seems to be achieved by ligand binding, which can switch on inhibition (FcγRII), enhance inhibition (CD22), or even turn off inhibition (CD72). These different strategies enable the B cell to tightly control the strength of the mIg signal in response to the microenvironment. The mechanisms of signal enhancement by CD19 and signal inhibition by CD22 and other inhibitory molecules are discussed in this chapter.