Lipid raft-dependent plasma membrane repair interferes with the activation of B lymphocytes.

Abstract

Cells rapidly repair plasma membrane (PM) damage by a process requiring Ca(2+)-dependent lysosome exocytosis. Acid sphingomyelinase (ASM) released from lysosomes induces endocytosis of injured membrane through caveolae, membrane invaginations from lipid rafts. How B lymphocytes, lacking any known form of caveolin, repair membrane injury is unknown. Here we show that B lymphocytes repair PM wounds in a Ca(2+)-dependent manner. Wounding induces lysosome exocytosis and endocytosis of dextran and the raft-binding cholera toxin subunit B (CTB). Resealing is reduced by ASM inhibitors and ASM deficiency and enhanced or restored by extracellular exposure to sphingomyelinase. B cell activation via B cell receptors (BCRs), a process requiring lipid rafts, interferes with PM repair. Conversely, wounding inhibits BCR signaling and internalization by disrupting BCR-lipid raft coclustering and by inducing the endocytosis of raft-bound CTB separately from BCR into tubular invaginations. Thus, PM repair and B cell activation interfere with one another because of competition for lipid rafts, revealing how frequent membrane injury and repair can impair B lymphocyte-mediated immune responses.

• Authors: Heather Miller, Thiago Castro-Gomes, Matthias Corrotte, Christina Tam, Timothy K Maugel, Norma W Andrews, Wenxia Song
• Journal: The Journal of cell biology (J Cell Biol) Vol. 211 Issue 6 Pg. 1193-205 (Dec 21 2015) ISSN: 1540-8140 [Electronic] United States
• PMID: 26694840 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Miller et al.

Chemical References

• Calcium

Topics

• Animals
• B-Lymphocytes (immunology, pathology)
• Calcium (metabolism)
• Lymphocyte Activation
• Membrane Microdomains (metabolism)
• Mice
• Mice, Inbred C57BL
• Spleen (cytology, metabolism)