This chapter primarily deals with the basic signal transduction pathways that are activated in response to binding of antigen to BCRs expressed on mature, quiescent B cells. The BCR complex is composed of an antigen recognition structure, membrane immunoglobulin (mIg), and an associated signal transducing heterodimer. Membrane Ig consists of two heavy chains and two light chains that are disulfide bonded to one another to form the mature antigen recognition structure. The transmembrane region of mIg heavy chains is thought to assume an α-helical conformation in the membrane in which one face of the α-helix is composed of highly conserved hydrophilic amino acid residues that mediate the interaction with the Igα-/? heterodimer. The other face of the α-helix is specific to each of the mIg isotypes, and contains several hydrophilic amino acid residues with large polar side groups. Binding of antigen to the complex is thought to cause a conformational change in the resting BCR oligomer such that SHP-1 activity is attenuated, possibly by causing the protein tyrosine phosphatases (PTP) to become physically dissociated from the BCR complex. Dissociation of SHP-1 would presumably favor a net increase in tyrosine phosphorylation of Igβ/χ leading to initiation of signal transduction and cellular activation. Binding of antigen causes a rapid translocation of the BCR to glycosphingolipid-enriched microdomains (GEM) within the plasma membrane. These microdomains are enriched for Src family protein tyrosine kinases (PTK) including Lyn, and the translocation of the BCR into GEM physically localizes the complex with Src PTKs, thereby promoting tyrosine phosphorylation of Igβ/χ by Lyn. © 2010 Elsevier Inc. All rights reserved.