Regulation of differentiation of peritoneal B-1a (CD5+) B cells. Activated peritoneal macrophages release prostaglandin E2, which inhibits IgM secretion by peritoneal B-1a cells.
The B-1a (CD5+) subset of B cells comprises the majority of B cells in the peritoneal cavity and is implicated in the pathogenesis of certain autoimmune diseases and lymphoproliferative disorders. When we stimulated purified B-1a cells with LPS, they produced more than four times as much IgM as similarly stimulated whole peritoneal cells (containing the same number of B-1a cells). Reconstitution experiments using FACS-purified peritoneal cell populations revealed that resident peritoneal macrophages (Mac1+, B220-) profoundly inhibited the LPS response of peritoneal B-1a cells. Culture of B-1a cells with peritoneal macrophages at a ratio of 3:1 (reflecting the in vivo ratio) resulted in a fivefold or greater reduction in the IgM response to LPS. LPS activation of macrophages resulted in production of a soluble factor that inhibited LPS-induced B cell differentiation by 86% when used at a concentration of 5%. When [3H]arachidonic acid-pulsed macrophages were stimulated with LPS, the major arachidonic acid metabolite secreted was PGE2 (a potent inhibitor of B cell differentiation). The inhibitory capacity of the macrophage-derived supernatant was reversed by the addition of anti-PGE2. These findings indicate that macrophage-derived PGE2 functions as an important regulator of polyclonal response of B-1a cells to LPS.
Chace
J H
JH
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
Fleming
A L
AL
Gordon
J A
JA
Perandones
C E
CE
Cowdery
J S
JS
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D018956:CD5 Antigens; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D015232:Dinoprostone / Q000096:biosynthesis* / Q000502:physiology; D005260:Female; D007075:Immunoglobulin M / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D051379:Mice; D008811:Mice, Inbred DBA
D015703:Antigens, CD; D018956:CD5 Antigens; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D015232:Dinoprostone