Membrane cholesterol content accounts for developmental differences in surface B cell receptor compartmentalization and signaling.
Recent studies argue for an important role for cholesterol in maintaining plasma membrane heterogeneity and influencing a variety of cellular processes, including signaling, adhesion, and permeability. Here, we document that tolerance-sensitive transitional immature B cells maintain significantly lower membrane unesterified cholesterol levels than mature-stage splenic B cells. In addition, the relatively low level of cholesterol in transitional immature B cells impairs compartmentalization of their B cell receptor (BCR) into cholesterol-enriched domains following BCR aggregation and reduces their ability to sustain certain aspects of BCR signaling as compared with mature B cells. These studies establish an unexpected difference in the lipid composition of peripheral transitional immature and mature B cells and point to a determining role for development-associated differences in cholesterol content for the differential responses of these B cells to BCR engagement.
Karnell
Fredrick G
FG
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6160, USA.
Brezski
Randall J
RJ
King
Leslie B
LB
Silverman
Michael A
MA
Monroe
John G
JG
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002451:Cell Compartmentation / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002462:Cell Membrane / Q000378:metabolism*; D016764:Cell Polarity / Q000276:immunology; D002784:Cholesterol / Q000378:metabolism* / Q000494:pharmacology; D003902:Detergents; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011940:Receptor Aggregation / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D012995:Solubility; D013154:Spleen / Q000166:cytology
D003902:Detergents; D008563:Membrane Lipids; D011947:Receptors, Antigen, B-Cell; D002784:Cholesterol