The influence of CD40 on the association of the B cell antigen receptor with lipid rafts in mature and immature cells.
Cholesterol- and sphingolipid-rich membrane microdomains termed lipid rafts appear to play a central role in B cell activation. In mature B cells, signaling through the B cell antigen receptor(BCR) is initiated from within rafts and leads to activation. In immature B cells, the BCR is excluded from rafts and signaling leads to apoptosis. CD40, a member of the tumor necrosis receptor family, is expressed by B cells throughout development and has been shown to influence the results of the engagement of antigen by the BCR in both mature B and immature B cells. Here evidence is provided that CD40 is excluded from the lipid rafts of both mature and immature B cells and remains excluded from rafts even after cross-linking. Nevertheless, in mature B cells CD40 signaling influences the association of the BCR with rafts resulting in an increase in the amount of BCR that translocates into rafts following ligand binding and a subsequent acceleration of the movement of the BCR from rafts. In immature B cells, the cross-linked BCR remains excluded from rafts in the presence of CD40 signaling, conditions under which BCR-induced apoptosis is blocked. These results indicate that CD40 functions outside lipid rafts to influence raft-dependent events in mature B cells and raft-independent events in immature B cells.
Malapati
S
S
Department of Biochemistry, Molecular Biology and Cell Biology Northwestern University, Evanston, IL, USA.
Pierce
S K
SK
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D019013:CD40 Antigens / Q000502:physiology*; D021962:Membrane Microdomains / Q000378:metabolism*; D051379:Mice; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D019013:CD40 Antigens; D011947:Receptors, Antigen, B-Cell