Engagement of the Human Pre-B Cell Receptor Generates a Lipid Raft–Dependent Calcium Signaling Complex

• Published in: Immunity (Cambridge, Mass.) Mass.), 2000-08, Vol.13 (2), p.243-253
• Main Authors: Guo, Beichu, Kato, Roberta M, Garcia-Lloret, Maria, Wahl, Matthew I, Rawlings, David J
• Format: Article
• Language: English
• Subjects: AB-cell receptor; B-Lymphocytes - cytology; B-Lymphocytes - physiology; Calcium - physiology; Cell Line; Cell Lineage - physiology; Humans; Immunoglobulin Light Chains - physiology; Lipids - physiology; Membrane Glycoproteins - physiology; Pre-B Cell Receptors; Receptors, Antigen, B-Cell; Signal Transduction - physiology
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/S1074-7613(00)00024-8

Pre-B cell receptor (pre-BCR) expression is critical for B lineage development. The signaling events initiated by the pre-BCR, however, remain poorly defined. We demonstrate that lipid rafts are the major functional compartment for human pre-B cell activation. A fraction of pre-BCR was constitutively raft associated, and receptor engagement enhanced this association. These events promoted Lyn activation and Igβ phosphorylation and led to the generation of a raft-associated signaling module composed of tyrosine phosphorylated Lyn, Syk, BLNK, PI3K, Btk, VAV, and PLCγ2. Formation of this module was essential for pre-BCR calcium signaling. Together, these observations directly link the previously identified genetic requirement for the components of this module in B lineage development with their functional role(s) in human pre-BCR signaling.